A randomised controlled trial comparing umbilical cord milking to delayed cord clamping at birth in preterm infants 28-36 weeks gestational age.

Delayed cord clamping (DCC) is an established practice in perinatology with multiple benefits. However, in instances where the implementation of DCC is not viable, it needs alternatives, especially during caesarean deliveries. A non-inferiority randomized, non-blinded, trial was conducted at a tertiary care referral unit in South India among the preterm newborns (28-36 weeks) randomized to DCC as opposed to intact-umbilical cord milking (UCM). The primary objective was to compare the mean haemoglobin values between the two groups, and the secondary outcome was to compare death and/or major IVH (> Grade II). Of the 132 eligible newborn infants, 99 were randomized to two study groups. Of the 59 and 40 randomised to UCM and DCC, 54 and 36 received the allocated intervention respectively. Preterm infants who underwent UCM had significantly higher haemoglobin (19.97 ± 1.44) as compared to DCC group (18.62 ± 0.98) p-0.0001. The rates of mortality and/or major IVH were comparable between the two groups. CONCLUSION: UCM may be a feasible alternative to DCC especially in settings where the latter is not achievable, without increasing the risk of adverse effects to the preterm infants, this finding needing further confirmation with larger sample. TRIAL REGISTRATION: CTRI (Clinical Trial Registry-India) registration number: CTRI/2020/04/024566 (registered prospectively on 13/04/2020). WHAT IS KNOWN: • Delayed cord clamping (DCC) is recommended as a standard of care for all the stable term and preterm newborn babies at birth. WHAT IS NEW: • Intact umbilical cord milking may be a reasonable choice of cord management when DCC is unsuccessful, without increasing adverse effects for the new born.

Influence of umbilical cord clamping time on cerebral oxygenation and early cardiac function in term infants.

BACKGROUND: Delayed cord clamping is the standard of care for both term and preterm infants worldwide. The aim of this study was to evaluate the effect of 60-second or 180-second delayed cord clamping during labor on cerebral oxygenation and cardiac function. METHODS: Healthy newborns were divided into two groups: a 60-second delay in cord clamping (60-s DCC) and a 180-second delay in cord clamping (180-s DCC) at birth. Pulse oximetry and cerebral near-infrared spectroscopy (cNIRS) probes were placed during postnatal care. A total of 84 healthy newborns were included in this study. Preductal oxygen saturation (SpO2), heart rate, and cNIRS values were recorded at 5 and 10 minutes after delivery. The cardiac function of the infants was assessed by echocardiography at 3-7 days postnatally. RESULTS: There was no significant difference between the groups in SpO2 and cNIRS values at 5 and 10 min. While there was no significant difference in the number of neonates with targeted SpO2 at the 5th and 10th min and targeted cNIRS values at the 10th min, there was a significant difference in the number of neonates with target cNIRS values at the 5th min between groups (p <  0.001). Echocardiographic findings showed that pulmonary flow velocity was increased in the 180-s DCC group; the difference was statistically significant (p = 0.04). CONCLUSION: Our results showed that the number of infants with normal cNIRS values regarding cerebral oxygenation was higher in the 180-s DCC group. The pulmonary flow velocity was significantly increased in the 180-s DCC group in terms of echocardiographic findings.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. METHODS: Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). RESULTS: Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. CONCLUSION: We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Short-term outcomes after selective shunt during carotid endarterectomy: A propensity score matching analysis / Resultados a corto plazo después de shunting selectivo durante la endarterectomía carotídea con anestesia regional: un análisis de propensity score-matching

Introduction and objectives: Carotid cross-clamping during carotid endarterectomy might lead to intraoperative neurologic deficits, increasing stroke/death risk. If deficits are detected, carotid shunting has been recommended to reduce the risk of stroke. However, shunting may sustain a specific chance of embolic events and subsequently incurring harm. Current evidence is still questionable regarding its clear benefit. The aim is to determine whether a policy of selective shunt impacts the complication rate following an endarterectomy. Material and methods: From January 2013 to May 2021, all patients undergoing carotid endarterectomy under regional anesthesia with intraoperative neurologic alteration were retrieved. Patients submitted to selective shunt were compared to a non-shunt group. A 1:1 propensity score matching (PSM) was performed. Differences between the groups and clinical outcomes were calculated, resorting to univariate analysis. Results: Ninety-eight patients were selected, from which 23 were operated on using a shunt. After PSM, 22 non-shunt patients were compared to 22 matched shunted patients. Concerning demographics and comorbidities, both groups were comparable to pre and post-PSM, except for chronic heart failure, which was more prevalent in shunted patients (26.1%, P=0.036) in pre-PSM analysis. Regarding 30-day stroke and score Clavien–Dindo≥2, no significant association was found (P=0.730, P=0.635 and P=0.942, P=0.472, correspondingly, for pre and post-PSM). Conclusions: In this cohort, resorting to shunting did not demonstrate an advantage regarding 30-day stroke or a Clavien–Dindo≥2 rates. Nevertheless, additional more extensive studies are mandatory to achieve precise results concerning the accurate utility of carotid shunting in this subset of patients under regional anesthesia.(AU)

Introducción y objetivos: El pinzamiento carotídeo durante la endarterectomía carotídea podría provocar déficits neurológicos intraoperatorios, lo que aumenta el riesgo de accidente cerebrovascular/muerte. Si se detectan déficits, se ha recomendado la derivación carotídea para reducir el riesgo de accidente cerebrovascular. Sin embargo, la derivación puede sostener una posibilidad específica de eventos embólicos y, posteriormente, provocar daños. La evidencia actual aún es cuestionable con respecto a su claro beneficio. El objetivo es determinar si una política de derivación selectiva afecta la tasa de complicaciones después de una endarterectomía. Material y métodos: Desde enero de 2013 hasta mayo de 2021 se recuperaron todos los pacientes sometidos a endarterectomía carotídea bajo anestesia regional con alteración neurológica intraoperatoria. Los pacientes sometidos a derivación selectiva se compararon con un grupo sin derivación. Se realizó una coincidencia de puntuación de propensión (PSM) 1:1. Se calcularon las diferencias entre los grupos y los resultados clínicos recurriendo al análisis univariado. Resultados: Se seleccionaron 98 pacientes, de los cuales 23 fueron intervenidos mediante derivación. Después de la PSM se compararon 22 pacientes sin derivación con 22 pacientes emparejados con derivación. Con respecto a la demografía y las comorbilidades, ambos grupos fueron comparables a los de antes y después de la PSM, excepto por la insuficiencia cardíaca crónica, que fue más prevalente en los pacientes con derivación (26,1%, p=0,036) en el análisis previo a la PSM. En cuanto al accidente cerebrovascular a los 30 días y la puntuación de Clavien-Dindo≥2, no se encontró asociación significativa (p=0,730, p=0,635 y p=0,942, p=0,472, correspondientemente, para pre y post-PSM). Conclusiones: En esta cohorte recurrir a la derivación no demostró una ventaja con respecto a las tasas de ictus a los 30 días o Clavien-Dindo≥2...(AU)

Physiological-based cord clamping in very preterm infants: the Aeration, Breathing, Clamping 3 (ABC3) trial-statistical analysis plan for a multicenter randomized controlled trial.

BACKGROUND: Mortality, cerebral injury, and necrotizing enterocolitis (NEC) are common complications of very preterm birth. An important risk factor for these complications is hemodynamic instability. Pre-clinical studies suggest that the timing of umbilical cord clamping affects hemodynamic stability during transition. Standard care is time-based cord clamping (TBCC), with clamping irrespective of lung aeration. It is unknown whether delaying cord clamping until lung aeration and ventilation have been established (physiological-based cord clamping, PBCC) is more beneficial. This document describes the statistical analyses for the ABC3 trial, which aims to assess the efficacy and safety of PBCC, compared to TBCC. METHODS: The ABC3 trial is a multicenter, randomized trial investigating PBCC (intervention) versus TBCC (control) in very preterm infants. The trial is ethically approved. Preterm infants born before 30 weeks of gestation are randomized after parental informed consent. The primary outcome is intact survival, defined as the composite of survival without major cerebral injury and/or NEC. Secondary short-term outcomes are co-morbidities and adverse events assessed during NICU admission, parental reported outcomes, and long-term neurodevelopmental outcomes assessed at a corrected age of 2 years. To test the hypothesis that PBCC increases intact survival, a logistic regression model will be estimated using generalized estimating equations (accounting for correlation between siblings and observations in the same center) with treatment and gestational age as predictors. This plan is written and submitted without knowledge of the data. DISCUSSION: The findings of this trial will provide evidence for future clinical guidelines on optimal cord clamping management at birth. TRIAL REGISTRATION: ClinicalTrials.gov NCT03808051. Registered on 17 January 2019.

Impact of the Timing of Umbilical Cord Clamping on Maternal and Neonatal Outcomes in Saudi Arabia.

INTRODUCTION: The optimal time for umbilical cord clamping after delivery has been under debate for several decades. This study aimed to assess the time-dependent effects of umbilical cord clamping on maternal and neonatal outcomes. METHODS: An observational correlational design was used to recruit 161 pregnant women conveniently. Outcomes were observed and recorded using a structured checklist developed by the authors. Pregnant females aged ≥18 years, with uncomplicated delivery, and who were willing to participate were recruited. Exclusion criteria included stillbirths, newborns with congenital anomalies, newborns too small for their gestational age, intra-uterine growth restriction, nuchal cord, and meconium-stained liquor. RESULTS: The mean age of the participants was 29.93 ± 6 years. Early clamping (<1 minute) was performed for 93.8% of the participants with a mean of 29.58 ± 18 seconds. Delayed clamping was associated with a decrease in blood loss and the length of hospital stay in addition to an increase in first-minute APGAR score and neonatal temperature (P < 0.05). CONCLUSIONS: Delayed cord clamping was associated with improved maternal and neonatal outcomes.

Third stage of labor: evidence-based practice for prevention of adverse maternal and neonatal outcomes.

The third stage of labor is defined as the time period between delivery of the fetus through delivery of the placenta. During a normal third stage, uterine contractions lead to separation and expulsion of the placenta from the uterus. Postpartum hemorrhage is a relatively common complication of the third stage of labor. Strategies have been studied to mitigate the risk of postpartum hemorrhage, leading to the widespread implementation of active management of the third stage of labor. Initially, active management of the third stage of labor consisted of a bundle of interventions including administration of a uterotonic agent, early cord clamping, controlled cord traction, and external uterine massage. However, the effectiveness of these interventions as a bundle has been questioned, leading to abandonment of some components in recent years. Despite this, upon review of selected international guidelines, we found that the term "active management of the third stage of labor" was still used, but recommendations for and against individual interventions were variable and not necessarily supported by current evidence. In this review, we: (1) examine the physiology of the third stage of labor, (2) present evidence related to interventions that prevent postpartum hemorrhage and promote maternal and neonatal health, (3) review current global guidelines and recommendations for practice, and (4) propose future areas of investigation. The interventions in this review include pharmacologic agents to prevent postpartum hemorrhage, cord clamping, cord milking, cord traction, cord drainage, early skin-to-skin contact, and nipple stimulation. Treatment of complications of the third stage of labor is outside of the scope of this review. We conclude that current evidence supports the use of effective pharmacologic postpartum hemorrhage prophylaxis, delayed cord clamping, early skin-to-skin contact, and controlled cord traction at delivery when feasible. The most effective uterotonic regimens for preventing postpartum hemorrhage after vaginal delivery include oxytocin plus ergometrine; oxytocin plus misoprostol; or carbetocin. After cesarean delivery, carbetocin or oxytocin as a bolus are the most effective regimens. There is inconsistent evidence regarding the use of tranexamic acid in addition to a uterotonic compared with a uterotonic alone for postpartum hemorrhage prevention after all deliveries. Because of differences in patient comorbidities, costs, and availability of resources and staff, decisions to use specific prevention strategies are dependent on patient- and system-level factors. We recommend that the term "active management of the third stage of labor" as a combined intervention no longer be used. Instead, we recommend that "third stage care" be adopted, which promotes the implementation of evidence-based interventions that incorporate practices that are safe and beneficial for both the woman and neonate.

Characteristics of A-type voltage-gated K+ currents expressed on sour-sensing type III taste receptor cells in mice.

Sour taste is detected by type III taste receptor cells that generate membrane depolarization with action potentials in response to HCl applied to the apical membranes. The shape of action potentials in type III cells exhibits larger afterhyperpolarization due to activation of transient A-type voltage-gated K+ currents. Although action potentials play an important role in neurotransmitter release, the electrophysiological features of A-type K+ currents in taste buds remain unclear. Here, we examined the electrophysiological properties of A-type K+ currents in mouse fungiform taste bud cells using in-situ whole-cell patch clamping. Type III cells were identified with SNAP-25 immunoreactivity and/or electrophysiological features of voltage-gated currents. Type III cells expressed A-type K+ currents which were completely inhibited by 10 mM TEA, whereas IP3R3-immunoreactive type II cells did not. The half-maximal activation and steady-state inactivation of A-type K+ currents were 17.9 ± 4.5 (n = 17) and - 11.0 ± 5.7 (n = 17) mV, respectively, which are similar to the features of Kv3.3 and Kv3.4 channels (transient and high voltage-activated K+ channels). The recovery from inactivation was well fitted with a double exponential equation; the fast and slow time constants were 6.4 ± 0.6 ms and 0.76 ± 0.26 s (n = 6), respectively. RT-PCR experiments suggest that Kv3.3 and Kv3.4 mRNAs were detected at the taste bud level, but not at single-cell levels. As the phosphorylation of Kv3.3 and Kv3.4 channels generally leads to the modulation of cell excitability, neuromodulator-mediated A-type K+ channel phosphorylation likely affects the signal transduction of taste.

Extended period of ventilation before delayed cord clamping augments left-to-right shunting and decreases systemic perfusion at birth in preterm lambs.

Previous studies have suggested that an extended period of ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. However, it is unknown whether this greater rise in PA flow is accompanied by increases in left ventricular (LV) output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale (FO), with decreased systemic arterial perfusion. Using an established preterm lamb birth transition model, this study compared the effect of a short (∼40 s, n = 11), moderate (∼2 min, n = 11) or extended (∼5 min, n = 12) period of initial mechanical lung ventilation before DCC on flow probe-derived perinatal changes in PA flow, LV output, total systemic arterial blood flow, ductal shunting and FO shunting. The LV output was relatively stable during initial ventilation but increased after DCC, with similar responses in all groups. Systemic arterial flow patterns displayed only minor differences during brief and moderate periods of initial ventilation and were similar after DCC. However, an increase in PA flow was augmented with an extended initial ventilation (P < 0.001), owing to an earlier onset of left-to-right ductal and FO shunting (P < 0.001), and was accompanied by a pronounced reduction in total systemic arterial flow (P = 0.005) that persisted for 4 min after DCC (P ≤ 0.039). These findings suggest that, owing to increased left-to-right shunting and a greater reduction in systemic arterial perfusion, an extended period of ventilation before DCC does not result in greater perinatal circulatory benefits than shorter periods of initial ventilation in the birth transition. KEY POINTS: Previous studies suggest that an extended period of initial ventilation before delayed cord clamping (DCC) augments birth-related rises in pulmonary arterial (PA) blood flow. It is unknown whether this greater rise in PA flow is accompanied by an increased left ventricular output and systemic arterial perfusion or whether it reflects enhanced left-to-right shunting across the ductus arteriosus and/or foramen ovale, with decreased systemic arterial perfusion. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent a brief (∼40 s), moderate (∼2 min) or extended (∼5 min) period of ventilation before DCC. Perinatal changes in left ventricular output were similar in all groups, but extended initial ventilation augmented both perinatal increases in PA flow, owing to earlier onset and greater left-to-right ductal and foramen ovale shunting, and perinatal reductions in total systemic arterial perfusion. Extended ventilation before DCC does not confer a greater perinatal circulatory benefit than shorter periods of initial ventilation.

Early Breathing in Very Preterm Infants during Deferred Cord Clamping (DCC) Is Related to Gestational Age and Is Not Independently Associated with Important Neonatal Outcomes: A 5-Year Cohort Study.

Deferred cord clamping (DCC) has been associated with reduced mortality in preterm infants, and a period of at least 30 s has been recommended before clamping. However, preterm infants assessed as being in need of resuscitation have often had earlier cord clamping. In this study, we aimed to compare neonatal outcomes for preterm infants undergoing DCC who established early breathing movements compared to those who were not breathing. After a 5 yr recruitment period, we recently completed the ABC study, in which preterm infants <31 weeks undergoing 50 s of DCC who were not breathing by 15 s of age were randomised into two groups: one received intermittent positive pressure ventilation (IPPV) and the other was a standard group, which received no breathing support. The outcomes in the two groups were similar, and for the present analysis, the groups were combined. Infants in the ABC study were compared with the cohort excluded from the original ABC study because they were breathing by 15 s (called the Breathing Before Clamping or BBC group). There were significant differences in demographics between the ABC and BBC groups. Spontaneous preterm labour was more common in the BBC group, and these infants were more likely to be delivered vaginally. Gestational age and birth weight were significantly higher in the BBC group (p < 0.01). Soon after birth, Apgar scores were significantly higher in the BBC group, with a lower base deficit on first obtained blood gas, and a smaller proportion were intubated in the delivery room. Fewer BBC infants were hypothermic (<36.5 °C) on admission. Multivariate regression analysis indicated whether infants were breathing or not at 15 s of age was linked predominantly to gestation. Important neonatal outcomes and a composite of these outcomes (mortality, severe intraventricular haemorrhage, bronchopulmonary dysplasia) were not significantly different between the ABC and BBC groups (odds ratio for the composite outcome was 1.77 CI 0.84-3.76 corrected for gestation). For very preterm infants undergoing DCC, important neonatal outcomes were related to gestational age and not independently associated with early breathing. There was a small group (7% of total) who were deemed compromised at birth and did not undergo DCC. These infants had significantly worse neonatal outcomes.

Effect of an Airbag-selective Portal Vein Blood Arrester on the Liver after Hepatectomy: A New Technique for Selective Clamping of the Portal Vein.

OBJECTIVE: A novel technique was explored using an airbag-selective portal vein blood arrester that circumvents the need for an intraoperative assessment of anatomical variations in patients with complex intrahepatic space-occupying lesions. METHODS: Rabbits undergoing hepatectomy were randomly assigned to 4 groups: intermittent portal triad clamping (PTC), intermittent portal vein clamping (PVC), intermittent portal vein blocker with an airbag-selective portal vein blood arrester (APC), and without portal blood occlusion (control). Hepatic ischemia and reperfusion injury were assessed by measuring the 7-day survival rate, blood loss, liver function, hepatic pathology, hepatic inflammatory cytokine infiltration, hepatic malondialdehyde levels, and proliferating cell nuclear antigen levels. RESULTS: Liver damage was substantially reduced in the APC and PVC groups. The APC animals exhibited transaminase levels similar to or less oxidative stress damage and inflammatory hepatocellular injury compared to those exhibited by the PVC animals. Bleeding was significantly higher in the control group than in the other groups. The APC group had less bleeding than the PVC group because of the avoidance of portal vein skeletonization during hepatectomy. Thus, more operative time was saved in the APC group than in the PVC group. Moreover, the total 7-day survival rate in the APC group was higher than that in the PTC group. CONCLUSION: Airbag-selective portal vein blood arresters may help protect against hepatic ischemia and reperfusion injury in rabbits undergoing partial hepatectomy. This technique may also help prevent liver damage in patients requiring hepatectomy.

Methods for studying P2X4 receptor ion channels in immune cells.

The P2X4 receptor is a trimeric ligand-gated ion channel activated by adenosine 5'-triphosphate (ATP). P2X4 is present in immune cells with emerging roles in inflammation and immunity, and related disorders. This review aims to provide an overview of the methods commonly used to study P2X4 in immune cells, focusing on those methods used to assess P2RX4 gene expression, the presence of the P2X4 protein, and P2X4 ion channel activity in these cells from humans, dogs, mice and rats. P2RX4 gene expression in immune cells is commonly assessed using semi-quantitative and quantitative reverse-transcriptase-PCR. The presence of P2X4 protein in immune cells is mainly assessed using anti-P2X4 polyclonal antibodies with immunoblotting or immunochemistry, but the use of these antibodies, as well as monoclonal antibodies and nanobodies to detect P2X4 with flow cytometry is increasing. Notably, use of an anti-P2X4 monoclonal antibody and flow cytometry has revealed that P2X4 is present on immune cells with a rank order of expression in eosinophils, then neutrophils and monocytes, then basophils and B cells, and finally T cells. P2X4 ion channel activity has been assessed mainly by Ca2+ flux assays using the cell permeable Ca2+-sensitive dyes Fura-2 and Fluo-4 with fluorescence microscopy, spectrophotometry, or flow cytometry. However, other methods including electrophysiology, and fluorescence assays measuring Na+ flux (using sodium green tetra-acetate) and dye uptake (using YO-PRO-12+) have been applied. Collectively, these methods have demonstrated the presence of functional P2X4 in monocytes and macrophages, microglia, eosinophils, mast cells and CD4+ T cells, with other evidence suggestive of functional P2X4 in dendritic cells, neutrophils, B cells and CD8+ T cells.

A Novel Technique for the Management of Persistent Biliary Fistulas Developing After Liver Hydatid Cyst Surgeries: Drain Clamping Technique.

BACKGROUND: External biliary fistula, where the residual cyst is associated with the biliary tree, is one of the most common complications after liver hydatid cyst surgery. Surgical procedures become a consideration for patients in whom the biliary fistula persists despite all endoscopic procedures. However, reoperation for biliary fistula after hydatid cyst surgery leads to additional complications and increases morbidity and mortality. AIM: This study aims to treat persistent biliary fistulas that develop after liver hydatid cyst surgery using a simple noninvasive technique. MATERIALS AND METHODS: External drainage surgery was performed on 295 patients with liver hydatid cysts. Endoscopic treatment methods were used in patients who developed biliary fistula after surgery. Despite all endoscopic treatment methods, 14 patients developed persistent biliary fistulas. These patients were subsequently treated using the drain clamping technique. FINDINGS: All persistent fistulas occluded in 11.86 days (with a range of 8-20 days). No complications were observed in the one-year follow-up visits. CONCLUSION: Drain clamping, a novel approach to the treatment of persistent biliary fistulas developed despite all available endoscopic methods, can be safely used. This technique resulted in a complete recovery in patients without the need for surgical procedures.

Deferred cord clamping to improve neonatal blood values: A systematic review and meta-analysis.

BACKGROUND: Practices related to umbilical cord clamping at birth should be evidence-based. Deferred cord clamping, compared to immediate cord clamping, shows benefits for preterm neonates but this may also apply to healthy term neonates. Different blood sampling techniques are used to measure effect of deferred and immediate cord clamping. OBJECTIVE: To assess the statistical and effect size differences between blood biomarkers from umbilical cord and capillary blood samples of healthy term neonates following either immediate or deferred cord clamping. DESIGN: Systematic review and meta-analysis. METHODS: The databases PubMed, Medline, CENTRAL, CINAHL and EMBASE were systematically searched. We included studies with a randomised clinical trial design comparing deferred and immediate cord clamping among healthy term neonates born by a spontaneous vaginal birth, reporting on blood biomarkers. Studies including caesarean births and premature births/neonates were excluded. Study attributes, sampling technique, blood biomarkers, mean differences, and standard deviations were extracted. The standardised mean differences (SMD) and sampling errors were calculated for effect size estimation. Meta-analyses were performed if ≥2 studies reported the same outcome using RevMan 5. Subgroup analyses distinguished effects from umbilical cord and capillary blood samples. Moderator tests and publication bias analyses were performed using JASP. RESULTS: Fifteen studies were included for analysis. The biomarkers haematocrit, haemoglobin, and bilirubin were reported in ≥2 studies and thus eligible for pooling. No differences were found in haemoglobin (SMD -0.04, 95%CI -0.57 to 0.49) or bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) between umbilical cord blood samples collected after deferred or immediate cord clamping. Deferred cord clamping led to lower haematocrit values (SMD -0.3, 95%CI -0.53 to -0.07). Higher haematocrit (SMD 0.67, 95%CI 0.37 to 0.97) and haemoglobin values (SMD 0.76, 95%CI 0.56 to 0.97) from capillary blood samples, collected 2 to 72 h postpartum, showed when cord clamping was deferred. No effect was found on bilirubin values (SMD 0.13, 95%CI -0.03 to 0.28) irrespective of the sampling technique. CONCLUSIONS: Blood collected after deferred umbilical cord clamping showed increased haemoglobin and haematocrit values up to 72 h after birth, opposed to bilirubin values. Clinical evaluation of blood biomarkers from the umbilical cord shows different values compared to capillary blood. Sampling time and technique therefore seem essential in estimating the effects of deferred cord clamping. TWEETABLE ABSTRACT: This meta-analysis shows that sampling time and technique are essential in estimating the effects of deferred cord clamping on neonatal blood values.

Different electrophysiological profiles of genetically labelled dopaminergic neurons in the mouse midbrain and olfactory bulb.

Dopaminergic (DA) neurons play pivotal roles in diverse brain functions, spanning movement, reward processing and sensory perception. DA neurons are most abundant in the midbrain (Substantia Nigra pars compacta [SNC] and Ventral Tegmental Area [VTA]) and the olfactory bulb (OB) in the forebrain. Interestingly, a subtype of OB DA neurons is capable of regenerating throughout life, while a second class is exclusively born during embryonic development. Compelling evidence in SNC and VTA also indicates substantial heterogeneity in terms of morphology, connectivity and function. To further investigate this heterogeneity and directly compare form and function of midbrain and forebrain bulbar DA neurons, we performed immunohistochemistry and whole-cell patch-clamp recordings in ex vivo brain slices from juvenile DAT-tdTomato mice. After confirming the penetrance and specificity of the dopamine transporter (DAT) Cre line, we compared soma shape, passive membrane properties, voltage sags and action potential (AP) firing across midbrain and forebrain bulbar DA subtypes. We found that each DA subgroup within midbrain and OB was highly heterogeneous, and that DA neurons across the two brain areas are also substantially different. These findings complement previous work in rats as well as gene expression and in vivo datasets, further questioning the existence of a single "dopaminergic" neuronal phenotype.

Physiological-based cord clamping stabilised cardiorespiratory parameters in very low birth weight infants.

AIM: We investigated the influence of physiological-based cord clamping (PBCC) on cardiorespiratory stability in very low birth weight (VLBW) infants during the first 72 h of life. METHODS: This retrospective study comprised VLBW infants born at <32 + 0 weeks of gestation and admitted to the neonatal intensive care unit of the Medical University of Graz, Austria, from December 2014 to April 2021. VLBW infants delivered with PBCC were matched by gestational age and birth weight to delayed cord clamping controls. The PBCC group was stabilised after birth with an intact cord. Routine monitoring parameters were compared between the groups. RESULTS: We included 54 VLBW infants. The mean gestational ages of the PBCC group and controls were 27.4 ± 1.9 versus 27.4 ± 1.8 weeks (p = 0.87), and the mean birth weights were 912 ± 288 versus 915 ± 285 g (p = 0.96), respectively. The mean cord clamping time was 191 ± 78 s in the PBCC group. Heart rate was lower in the PBCC group during the first 3 days after birth, reaching significance by 10 h. Other monitoring parameters did not reveal any differences between the two groups. CONCLUSION: PBCC stabilised cardiorespiratory parameters in VLBW infants. The lower heart rate in the PBCC group suggested higher blood volume following intact cord resuscitation.

Delayed cord clamping vs cord milking in elective cesarean delivery at term: a randomized controlled trial.

BACKGROUND: Delayed cord clamping has significant beneficial effects on the neonate and its transition to extrauterine life and, therefore, is common practice at vaginal births in the Netherlands. In 2015, 16% of neonates were born via cesarean delivery; moreover, in 81% of these cases, the umbilical cord was clamped and cut immediately. Neonatal benefits of delayed cord clamping are an increased circulating volume of 25 to 30 mL/kg, leading to a higher preload of both the right and left ventricles during the transition from umbilical circulation to pulmonary circulation, thus maintaining a stable left ventricle output, and to higher neonatal hemoglobin and hematocrit levels 24 to 48 hours after birth. Currently, little is known about whether the abovementioned neonatal benefits of delayed cord clamping could apply to neonates delivered by cesarean delivery. In these cases, possible negative effects on neonatal outcomes (ie, neonatal hypothermia, lower Apgar scores, and hyperbilirubinemia) and maternal outcomes (ie, increased maternal blood loss and higher postoperative infection rate) should also be taken into consideration. OBJECTIVE: This study aimed to determine whether clamping the umbilical cord after 2 minutes is superior to cord milking during elective cesarean deliveries at term, taking both short- and long-term neonatal and maternal outcomes into consideration, and to determine whether cord milking could be an appropriate alternative to delayed cord clamping. STUDY DESIGN: A randomized controlled trial was conducted in a large secondary care center in the Netherlands (Amphia Hospital in Breda) from October 2020 to April 2022. A total of 115 patients who underwent an elective cesarean delivery between 37 0/7 and 41 6/7 weeks of gestation were included. The primary outcomes were neonatal hemoglobin and hematocrit levels at 48 hours after birth. The secondary outcomes were divided into neonatal and maternal outcomes. RESULTS: After randomization, 58 participants were treated with cord milking, and 57 participants were treated with delayed cord clamping. There was no significant difference in demographic characteristics between both groups. There was no significant difference in the primary outcomes, with a mean hemoglobin level 48 hours after birth of 12.1 mmol/L in the delayed cord clamping group and 12.2 mmol/L in the cord milking group (P=.80). Regarding our secondary outcomes, there was no significant difference regarding Apgar score, neonatal body temperature, maternal blood loss, and postoperative infection rate between our intervention groups. CONCLUSION: Hemoglobin and hematocrit levels at 48 hours after birth showed no significant difference when comparing delayed cord clamping with cord milking. Delayed cord clamping did not lead to increased maternal blood loss or postoperative infections compared with a method with a much shorter timeframe between delivery and clamping of the umbilical cord, namely, cord milking. In addition, delayed cord clamping did not lead to a lower Apgar score or neonatal temperature compared with cord milking. Our research suggests that delayed cord clamping can be safely performed during elective cesarean deliveries at term. If intraoperative circumstances do not allow for delayed cord clamping, cord milking can be an appropriate alternative for the neonate at term.

Transmission of high arterial pressure into renal microvessels during venous-clamping augments ischaemia/reperfusion-induced acute kidney injury in anaesthetized rats.

AIM: In two recent studies, we observed that a 30-min renal vein clamping caused formation of interstitial haemorrhagic congestion in ischaemic and ischaemic/reperfused kidney along with the development of severer acute kidney injury (AKI) than renal artery or pedicle clamping. It was suggested that the transmission of high arterial pressure into renal microvessels during vein occlusion probably causes the occurrence of interstitial haemorrhagic congestion that augments AKI. The present investigation aimed to evaluate this suggestion by reducing renal perfusion pressure (RPP) during renal venous occlusion. METHODS: Anaesthetized male Sprague-Dawley rats were divided into three groups (n = 8), which underwent a 2-h reperfusion period following 30-min bilateral renal venous clamping along with reduced RPP (VIR-rRPP group) or without reduced RPP (VIR group) and an equivalent period after sham-operation (Sham group). RESULTS: The VIR-rRPP group compared with VIR group had lower levels of kidney malondialdehyde and tissue damages as epithelial injuries of proximal tubule and thick ascending limb, vascular congestion, intratubular cast and oedema, along with the less reductions in renal blood flow, creatinine clearance, Na+ -reabsorption, K+ and urea excretion, urine osmolality and free-water reabsorption. Importantly, the formation of intensive interstitial haemorrhagic congestion in the VIR group was not observed in the VIR-rRPP group. CONCLUSION: These results indicate that the transmission of high arterial pressure into renal microvessels during venous occlusion leads to rupturing of their walls and the formation of interstitial haemorrhagic congestion, which has an augmenting impact on ischaemia/reperfusion-induced renal structural damages and haemodynamic, excretory and urine-concentrating dysfunctions.

[Interpretation of 2023 American Heart Association and American Academy of Pediatrics focused update on neonatal resuscitation guidelines]. / 2023美国心脏协会与美国儿科学会新生儿复苏指南要点更新解读.

In November 2023, the American Heart Association and the American Academy of Pediatrics jointly released key updates to the neonatal resuscitation guidelines based on new clinical evidence. This update serves as an important supplement to the "Neonatal resuscitation: 2020 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care". The aim of this paper is to outline the key updates and provide guidance on umbilical cord management and the selection of positive pressure ventilation equipment and its additional interfaces in neonatal resuscitation.