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.

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.

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.

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.

Does delayed cord clamping result in higher maternal blood loss in primary cesarean sections? A retrospective comparative study.

OBJECTIVES: The University Hospital Basel implemented delayed umbilical cord clamping of 30-60 s in all laboring women on April 1, 2020. This practice has been widely researched showing substantial benefit for the neonate. Few studies focused on maternal blood loss. The objective of our retrospective comparative study was to assess the impact of immediate vs. delayed cord clamping on maternal blood loss in primary scheduled cesarean sections. METHODS: We analyzed data of 98 women with singleton gestations undergoing primary scheduled cesarean section at term. Data from procedures with early cord clamping (ECC) were compared to those after implementation of delayed cord clamping (DCC). Primary outcomes were perioperative change in maternal hemoglobin levels, estimated and calculated blood loss. Secondary outcomes included duration of cesarean section and neonatal data. RESULTS: There was a statistically significant difference in the mean perioperative decline of hemoglobin of 10.4 g/L (SD=7.92) and 18.7 g/L (SD=10.4) between the ECC and DCC group, respectively (p<0.001). The estimated (482 mL in ECC vs. 566 mL in DCC (p=0.011)) and the calculated blood loss (438 mL in ECC vs. 715 mL in DCC (p=0.002)) also differed significantly. Secondary outcomes showed no significant differences. CONCLUSIONS: In our study DCC resulted in a statistically significant higher maternal blood loss. In our opinion the widely researched neonatal benefit of DCC outweighs the risk of higher maternal blood loss in low-risk patients. However, maternal risks must be minimized, improvements to preoperative blood management and operative techniques are required.

Effect of administration routes of oxytocin on hemoglobin in neonates with delayed umbilical cord clamping: a multi-centre randomized controlled clinical trial.

PURPOSE: To evaluate the effect of intravenous infusion versus intramyometrial injection of oxytocin on hemoglobin levels in neonates with delayed umbilical cord clamping during cesarean section. METHODS: The multi-centre randomized controlled trial was performed at three hospitals from February to June 2023. Women with term singleton gestations scheduled for cesarean delivery were allocated to receive an intravenous infusion of 10 units of oxytocin or a myometrial injection of 10 units of oxytocin during the surgery. The primary outcome was neonatal hemoglobin at 48 to 96 h after birth. Secondary outcomes were side-effects of oxytocin, postpartum haemorrhage, phototherapy for jaundice, feeding at 1 month, maternal and neonatal morbidity and re-admissions. RESULTS: A total of 360 women were randomized (180 women in each group). The mean neonatal hemoglobin did not show a significant difference between the intravenous infusion group (194.3 ± 21.7 g/L) and the intramyometrial groups (195.2 ± 24.3 g/L) (p = 0.715). Secondary neonatal outcomes, involving phototherapy for jaundice, feeding at 1 month and neonatal intensive care unit admission were similar between the two groups. The maternal outcomes did not differ significantly between the two groups, except for a 200 mL higher intraoperative infusion volume observed in the intravenous group compared to the intramyometrial group. CONCLUSION: Among women undergoing elective cesarean delivery of term singleton pregnancies, there was no significant difference in neonatal hemoglobin at 48 to 96 h after birth between infants with delayed cord clamping, whether the oxytocin was administrated by intravenous infusion or intramyometrial injection. TRIAL REGISTRATION: Chinese Clinical trial registry: ChiCTR2300067953 (1 February 2023).

Placental cord drainage vs delayed cord clamping at elective caesarean section: A randomised controlled trial.

BACKGROUND: Placental cord drainage (PCD) after vaginal birth accelerates placental delivery by 2.85 minutes, but reduces blood loss by only 77 mL. AIMS: To determine if PCD at elective caesarean section accelerates placental delivery, compared to delayed cord clamping (DCC). MATERIALS AND METHODS: This randomised controlled trial randomised 100 women undergoing elective caesarean sections to receive either PCD for 60 sec after birth, or DCC for 60 sec. The primary outcome was time from birth until placental delivery. Secondary outcomes included estimated blood loss (EBL), postoperative haemoglobin drop, rates of postpartum haemorrhage (PPH), manual removal of placenta and blood transfusion. RESULTS: There was no significant difference in timing of placental delivery (PCD 122 sec vs DCC 123.5 sec, P = 0.717). There were no significant differences in EBL (PCD 425 mL vs DCC 400 mL, P = 0.858), postoperative haemoglobin drop (PCD 12 g/L vs DCC 15 g/L, P = 0.297), PPH rate (PCD 45.8% vs DCC 44.4%, P = 0.893, relative risk (RR) 1.03, 95% confidence interval (CI) 0.66-1.62), manual removal rate (PCD 2.1% vs DCC 4.4%, P = 0.609, RR 0.47, 95% CI 0.04-4.99) or transfusion rate (PCD 4.2% vs DCC 0%, P = 0.495). CONCLUSIONS: PCD did not accelerate placental delivery at caesarean compared with DCC. Given that both PCD and DCC groups had faster placental deliveries than quoted in the literature at caesarean (200 sec), it could be postulated that DCC is mimicking the effect of PCD through passive transfusion to the neonate. This supports routine use of DCC at elective caesarean section.

Hemodynamic Changes with Umbilical Cord Milking in Nonvigorous Newborns: A Randomized Cluster Cross-over Trial.

OBJECTIVE: To assess the hemodynamic safety and efficacy of umbilical cord milking (UCM) compared with early cord clamping (ECC) in nonvigorous newborn infants enrolled in a large multicenter randomized cluster-crossover trial. STUDY DESIGN: Two hundred twenty-seven nonvigorous term or near-term infants who were enrolled in the parent UCM vs ECC trial consented for this substudy. An echocardiogram was performed at 12 ± 6 hours of age by ultrasound technicians blinded to randomization. The primary outcome was left ventricular output (LVO). Prespecified secondary outcomes included measured superior vena cava (SVC) flow, right ventricular output (RVO), peak systolic strain, and peak systolic velocity by tissue Doppler examination of the RV lateral wall and the interventricular septum. RESULTS: Nonvigorous infants receiving UCM had increased hemodynamic echocardiographic parameters as measured by higher LVO (225 ± 64 vs 187 ± 52 mL/kg/min; P < .001), RVO (284 ± 88 vs 222 ± 96 mL/kg/min; P < .001), and SVC flow (100 ± 36 vs 86 ± 40 mL/kg/min; P < .001) compared with the ECC group. Peak systolic strain was lower (-17 ± 3 vs -22 ± 3%; P < .001), but there was no difference in peak tissue Doppler flow (0.06 m/s [IQR, 0.05-0.07 m/s] vs 0.06 m/s [IQR, 0.05-0.08 m/s]). CONCLUSIONS: UCM increased cardiac output (as measured by LVO) compared with ECC in nonvigorous newborns. Overall increases in measures of cerebral and pulmonary blood flow (as measured by SVC and RVO flow, respectively) may explain improved outcomes associated with UCM (less cardiorespiratory support at birth and fewer cases of moderate-to-severe hypoxic ischemic encephalopathy) among nonvigorous newborn infants.

Implementing intact cord resuscitation in very preterm infants: feasibility and pitfalls.

The purpose of this study is to evaluate the feasibility of intact cord resuscitation (ICR) in very preterm infants using a custom-equipped mobile resuscitation trolley (LifeStart®). We collected maternal and neonatal data of all inborn infants < 32 weeks eligible for ICR per our protocol over 9 months from ICR implementation. We compared rates of ICR between the beginning and the end of the study period. We reviewed maternal and neonatal adverse events related to the procedure and direct outcomes. In order to assess potential quality improvements related to the procedure, we collected the same data in the infants born in the 9-month period preceding ICR implementation. Out of 44 infants born < 32 weeks during the period, 27 were eligible for ICR. Failure to initiate ICR occurred in 9/27, exclusively in the first 5.5 months of the study. In one infant, ICR was interrupted prior to 2 min due to placental abruption. No ICR procedure had to be interrupted due to insufficient cord length. Among the 18 infants who completed ICR, cord clamping timing increased significantly over the study period, from 3.0 [2.5-3.5] to 4.2 min [3.1-8.3] (p = 0.02). No significant maternal blood loss or wound complications were noted. No infant deaths were attributable to failure or direct consequence of ICR, and no infant experienced hypoxic respiratory failure (intubation, FiO2 ≥ 0.4), asphyxia (pH < 7.2), or blood pressure instability (< 2 SD) following stabilization. Hemoglobin level after cord clamping was higher in the ICR cohort than in the pre-implementation group. Seven out of 18 infants exposed to ICR had a temperature < 36.5 °C on admission.   Conclusion: ICR is feasible in very preterm infants. Temperature management requires special attention. Multidisciplinary simulation training before implementation and systematic post-implementation quality improvement meetings may significantly increase ICR program success. What is Known: • Because infants born < 32 weeks often require cardiorespiratory resuscitation at birth, they are not offered delayed cord clamping in the majority of neonatal intensive care units. • Recently, fully equipped mobile trolleys have been developed in order to allow bedside resuscitation with an intact cord. What is New: • Variable timing of cord clamping based on the infant's transition and respiratory stability, i.e., "physiology-based cord clamping," is safely achievable in very preterm infants. • Intact cord resuscitation requires specific equipment, operational protocols, and a high level of preparation from both obstetrical and neonatal teams, with a learning curve that can be streamlined by multidisciplinary simulation training.

Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial.

Recommendations for umbilical cord management in intrauterine growth-restricted (IUGR) neonates are lacking. The present randomized controlled trial compared hemodynamic effects of umbilical cord milking (UCM) with delayed cord clamping (DCC) in IUGR neonates > 28 weeks of gestation, not requiring resuscitation. One hundred seventy IUGR neonates were randomly allocated to intact UCM (4 times squeezing of 20 cm intact cord; n = 85) or DCC (cord clamping after 60 s; n = 85) immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24 ± 2 h. Secondary outcomes assessed were anterior cerebral artery (ACA) and superior mesenteric artery (SMA) blood flow indices, right ventricular output (RVO), regional cerebral oxygen saturation (CrSO2) and venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), incidences of in-hospital complications, need and duration of respiratory support, and hospital stay. SVC flow was significantly higher in UCM compared to DCC (111.95 ± 33.54 and 99.49 ± 31.96 mL/kg/min, in UCM and DCC groups, respectively; p < 0.05). RVO and ACA/SMA blood flow indices were comparable whereas CrSO2 was significantly higher in UCM group. Incidences of polycythemia and jaundice requiring phototherapy were similar despite significantly higher venous hematocrit and peak TSB in UCM group. The need for non-invasive respiratory support was significantly higher in UCM group though the need and duration of mechanical ventilation and other outcomes were comparable. CONCLUSIONS:  UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM. TRIAL REGISTRATION: Clinical trial registry of India (CTRI/2021/03/031864). WHAT IS KNOWN: • Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC). • An association between UCM and intraventricular hemorrhage in preterm neonates < 28 weeks of gestation is still being investigated. WHAT IS NEW: • Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates. • UCM also increases the need for non-invasive respiratory support compared to DCC.

Premature infants receiving delayed cord clamping with and without cord milking: a randomized control trial.

BACKGROUND: Preterm infants often have long hospital stays and frequent blood tests; they often develop anemia requiring multiple blood transfusions. Placental transfusion via delayed cord clamping (DCC) or umbilical cord milking (UCM) helps increase blood volume. We hypothesized umbilical cord milking (UCM), together with DCC, would be superior in reducing blood transfusions. OBJECTIVES: To compare the effects of DCC and DCC combined with UCM on hematologic outcomes among preterm infants. METHODS: One hundred twenty singleton preterm infants born at 280/7- 336/7 weeks of gestation at Thammasat University Hospital were enrolled in an open-label, randomized, controlled trial. They were placed into three groups (1:1:1) by a block-of-three randomization: DCC for 45 s, DCC with UCM performed before clamping (DCM-B), and DCC with UCM performed after clamping (DCM-A). The primary outcomes were hematocrit levels and number of infants receiving blood transfusions during the first 28 days of life. Intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC) were secondary outcomes. Analyses were performed with an intent-to-treat approach. RESULTS: One hundred twenty preterm infants were randomized. There was no statistically significant difference in neonatal outcomes; hematocrit on admission 54.0 ± 5.5, 53.3 ± 6.0, and 54.3 ± 5.8 (p = 0.88), receiving blood transfusions 25%, 20%, and 12.5% (p = 0.24), incidence of NEC 7.5, 0 and 10% (p = 0.78) in the DCC, DCM-B and DCM-A groups, respectively. There were no preterm infants with severe IVH, polycythemia, maternal or neonatal death. CONCLUSION: The placental transfusion techniques utilized, DCC and DCC combined with UCM, provided the same benefits for preterm infants born at GA 28 and 33 weeks in terms of reducing the need for RBC transfusions, severities of IVH and incidence of NEC without increasing comorbidity. TRIAL REGISTRATION: TCTR20190131002 . Registered 31 January 2019-Retrospectively registered.

The impact of early versus delayed cord clamping on hematological and cardiovascular changes in preterm newborns between 24 and 34 weeks' gestation: a randomized clinical trial.

PURPOSE: This study aimed to   investigate hematological and cardiac changes after early (ECC) versus delayed cord clamping (DCC) in preterm infants at 24-34 weeks of gestation. METHODS: Ninety-six healthy pregnant women were assigned randomly to the ECC (< 10 s postpartum, n = 49) or DCC (45-60 s postpartum, n = 47). Primary endpoint was evaluation of neonatal hemoglobin, hematocrit and bilirrubin levels within the first 7 days after birth. A postpartum blood test was performed in the mother and a neonatal echocardiography in the first week of life. RESULTS: We found differences in hematological parameters during the first week of life. On admission, the DCC group had higher hemoglobin levels than the ECC group (18.7 ± 3.0 vs. 16.8 ± 2.4, p < 0.0014) and higher hematocrit values (53.9 ± 8.0 vs. 48.8 ± 6.4, p < 0.0011). Around day 7 of life, hemoglobin levels were also higher in the DCC group compared with the ECC group (16.4 ± 3.8 vs 13.9 ± 2.5, p < 0.005), as was the hematocrit (49.3 ± 12.7 vs 41.2 ± 8.4, p < 0.0087). The need of transfusion was lower in the DCC compared to the ECC (8.5% vs 24.5%; OR: 0.29, 95% CI: 0.09-0.97, p < 0.036). The need for phototherapy was also higher in the DCC (80.9% vs 63.3%; OR: 0.23, 95% CI: 0.06-0.84, p < 0.026). No differences in cardiac parameters or maternal blood tests. CONCLUSION: DCC improved neonatal hematological parameters. No changes in cardiac function were found and maternal blood loss did not increase to require transfusion.

Comparing the safety and effectiveness of various umbilical cord milking techniques and delayed cord clamping in full-term and preterm infants: A systematic review and meta-analysis.

We compare the hematocrit, hemoglobin, need for transfusion, recurrent phototherapy, serum bilirubin level, and serum ferritin at different time frames for the umbilical cord milking (UCM) and delayed cord clamping (DCC) in both full-term and preterm infants. A comprehensive search through various databases aimed to compare UCM and DCC studies until May 2nd, 2023. Cochrane and NIH tools assessed RCTs and cohorts, respectively. Meta-analysis employed Review Manager 5.4 software, calculating MD and RR with 95% CIs for continuous and dichotomous data. We included 20 studies with a total of 5189 infants. Regarding preterm infants, hematocrit level showed no significant difference between intact Umbilical Cord Milking (iUCM) compared to DCC (MD = -0.24, 95% CI [-1.11, 0.64]). Moreover, Neonatal death incidence was significantly higher with the UCM technique in comparison to DCC (RR = 1.28, 95% CI [1.01 to 1.62]). Regarding term and late preterm infants, Hematocrit level showed no significant difference between the iUCM or cUCM techniques compared to DCC (MD = 0.21, 95% CI [-1.28 to 1.69]), (MD = 0.96, 95% CI [-1.02 to 2.95]), respectively. UCM led to a higher risk of neonatal death in preterm infants compared to DCC. However, the incidence of polycythemia was lower in the UCM group. Additionally, UCM was associated with higher rates of severe IVH events. Based on these findings, DCC may be preferred due to its lower incidence of severe IVH and neonatal death.

Nous comparons l'hématocrite, l'hémoglobine, le besoin de transfusion, la photothérapie récurrente, le taux de bilirubine sérique et la ferritine sérique à différentes périodes pour la traite du cordon ombilical (UCM) et le clampage retardé du cordon (DCC) chez les nourrissons nés à terme et prématurés. Une recherche complète dans diverses bases de données visait à comparer les études UCM et DCC jusqu'au 2 mai 2023. Les outils Cochrane et NIH ont évalué les ECR et les cohortes, respectivement. La méta-analyse a utilisé le logiciel Review Manager 5.4, calculant le MD et le RR avec des IC à 95 % pour les données continues et dichotomiques. Nous avons inclus 20 études portant sur un total de 5 189 nourrissons. Concernant les nourrissons prématurés, le niveau d'hématocrite n'a montré aucune différence significative entre la traite du cordon ombilical intact (iUCM) et la DCC (DM = -0,24, IC à 95 % [-1,11, 0,64]). De plus, l'incidence des décès néonatals était significativement plus élevée avec la technique UCM qu'avec la technique DCC (RR = 1,28, IC à 95 % [1,01 à 1,62]). Concernant les nourrissons à terme et peu prématurés, le niveau = 0,21, IC à 95 % [-1,28 à 1,69]), (DM = 0,96, IC à 95 % [-1,02 à 2,95]), respectivement. L'UCM a entraîné un risque plus élevé de décès néonatal chez les nourrissons prématurés par rapport au DCC. Cependant, l'incidence de la polyglobulie était plus faible dans le groupe UCM. De plus, l'UCM était associée à des taux plus élevés d'événements IVH graves. Sur la base de ces résultats, le DCC peut être préféré en raison de sa plus faible incidence d'IVH grave et de décès néonatals. d'hématocrite n'a montré aucune différence significative entre les techniques iUCM ou cUCM par rapport à la technique DCC (DM.

Divergent effects of initial ventilation with delayed cord clamping on systemic and pulmonary arterial flows in the birth transition of preterm lambs.

A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC followed by an asphyxial (∼2 min) cord clamp-to-ventilation (CC-V) interval. More recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45 s) CC-V interval, but it is unknown how ventricular output and central arterial blood flow effects of DCC compare with those of non-asphyxial ICC. Anaesthetized preterm fetal lambs instrumented with flow probes on major central arteries were ventilated for 97 (7) s (mean (SD)) before DCC at birth (n = 10), or underwent ICC 40 (6) s before ventilation (n = 10). Compared to ICC, initial ventilation and DCC was accompanied by (1) redistribution of a similar level of ascending aortic flow away from cephalic arteries and towards the aortic isthmus after ventilation; (2) a lower right ventricular output after cord clamping that was redistributed towards the lungs, thereby maintaining the absolute contribution of this output to a similar increase in pulmonary arterial flow after birth; and (3) a lower descending thoracic aortic flow after birth, related to a more rapid decline in phasic right-to-left ductal flow only partially offset by increased aortic isthmus flow. However, systemic arterial flows were similar between DCC and non-asphyxial ICC within 5 min after birth. These findings suggest that compared to non-asphyxial ICC, initial ventilation with DCC transiently redistributed central arterial flows, resulting in lower perinatal systemic arterial, but not pulmonary arterial, flows. KEY POINTS: A current view that delayed cord clamping (DCC) results in greater haemodynamic stability at birth than immediate cord clamping (ICC) is based on comparison of DCC vs. ICC with an asphyxial (∼2 min) cord clamp-to-ventilation (CC-V) interval. Recent data suggest that relatively minor perinatal differences in heart rate and blood pressure fluctuations exist between DCC and ICC with a non-asphyxial (<45 s) CC-V interval, but how central arterial blood flow effects of DCC compare with those of non-asphyxial ICC is unknown. Anaesthetized preterm fetal lambs instrumented with central arterial flow probes underwent initial ventilation for ∼90 s before DCC at birth, or ICC for ∼40 s before ventilation. Compared to non-asphyxial ICC, initial ventilation with DCC redistributed central blood flows, resulting in lower systemic, but not pulmonary, arterial flows during this period of transition. This flow redistribution was transitory, however, with systemic arterial flows similar between DCC and non-asphyxial ICC within minutes after birth.

The effect of placental transfusion on hemodynamics in premature newborns: a randomized controlled trial.

Despite of growing evidence of the beneficial effects of placental transfusion techniques, there is no available sufficient data about their effects on vulnerable hemodynamics and myocardium of premature infants. The purpose of this work is to study ventricular functions and hemodynamics after applying different placental transfusion techniques, delayed cord clamping (DCC), cut cord milking (C-UCM), and intact cord milking (I-UCM). Sixty-four infants delivered whether by C-section or vaginal delivery were randomly assigned to undergo C-UCM (20-30 cm), I-UCM (3-4 strippings), and DCC (30-60 s). Functional echocardiography was done on day 1 and day 3 of life for 57 infants. Primary outcome variable was superior vena cava flow measurement in infants having placental transfusion in the first 24 h of life and between 64 and 72 h. Secondary outcomes were other echocardiographic and clinical hemodynamic parameters, and biventricular functions in those infants. Of a total 196 preterm infants ≤ 32 weeks delivered in the study period, from January 2021 to August 2021, 57 infants were eligible and survived till the second examination. They were randomly assigned to the three groups. Neonates randomly assigned to DCC had significantly higher superior vena cava flow and lower right ventricular systolic function in the first 24 h of life. This finding vanished at day 3. Neonates undergone different methods of placental transfusions had similar hemoglobin, admission temperature, and mean blood pressure in the first 24 h of life. CONCLUSION: Despite their potential benefits, placental transfusions have shown to alter the hemodynamics and adversely affect myocardial function of premature neonates. TRIAL REGISTRATION: This trial was registered in the clinical trial gov NCT04811872. WHAT IS KNOWN: • Placental transfusion techniques might have benefits regarding prematurity- related morbidities and mortality. WHAT IS NEW: • Placental transfusion might adversely affect the myocardium and alter hemodynamics in premature infants.

Differential effects of delayed cord clamping on bilirubin levels in normal and diabetic pregnancies.

The purpose of the study is to investigate the effects of delayed cord clamping on bilirubin levels and phototherapy rates in neonates of diabetic mothers. This was a prospective study that enrolled pregnant women without pregnancy complications and those with diabetes. Their neonates were randomized in a 1:1 ratio to delayed cord clamping. The main outcomes were the neonatal transcutaneous bilirubin values on 2-4 days postpartum and the rate of requiring phototherapy in infants. A total of 261 pregnant women were included in the final analysis (132 women with diabetic pregnancies and 129 women with normal pregnancies). In diabetic pregnancies, neonatal bilirubin levels on the 2-4 days postpartum and phototherapy rates were significantly higher in the delayed cord clamping group than in the immediate cord clamping group (7.65 ± 1.83 vs 8.25 ± 1.96, P = 0.039; 10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.002; 11.54 ± 2.94 vs 12.83 ± 3.07 P = 0.024, 18.2% vs 6.3%, P = 0.042), while in normal pregnancies, there was no statistical difference in bilirubin values and phototherapy rates between the delayed cord clamping group and the immediate cord clamping group (P > 0.05). After receiving delayed cord clamping, bilirubin levels on the third postnatal day and the rate of requiring phototherapy in infants were higher in the diabetic pregnancy group than in the normal pregnancy group (10.35 ± 2.23 vs 11.54 ± 2.56, P = 0.013). CONCLUSION: Delayed cord clamping increased the risk of jaundice in newborns born to diabetic mothers, but had no effect in newborns from mothers with normal pregnancies. DCC may be a risk factor for increased bilirubin in infants of diabetic mothers. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04369313; date of registration: April 27, 2020 (retrospectively registered). WHAT IS KNOWN: • Delayed cord clamping had significant benefits for newborns by increasing neonatal hemoglobin levels and reducing the risk of neonatal anemia, etc. • Delayed cord clamping may lead to neonatal hyperemia, erythrocytosis, and hyperbilirubinemia, which increases the risk of neonatal jaundice. WHAT IS NEW: • Our trial focused on the differential effects of delayed cord clamping on jaundice in full-term newborns between diabetic pregnancies and normal pregnancies. And newborns of diabetic mothers who received delayed cord clamping had a significantly increased risk of jaundice compared to newborns with normal pregnancy. • Delayed cord clamping may be a risk factor for increased bilirubin levels in neonates of diabetic mothers.

Implementation of Delayed Cord Clamping in public health facilities: a case study from India.

BACKGROUND: Global and country specific recommendations on Delayed umbilical cord clamping (DCC) are available, though guidance on their implementation in program settings is lacking. In India, DCC (clamping not earlier than 1 min after birth) is a component in the package of services delivered as part of the India Newborn Action Plan (INAP) supported by Nutrition International (NI) in two states. The objective of this case study was to document the learnings from implementation of DCC in these two states and to understand the health system factors that affected its operationalization. METHODS: Mixed methods were followed. Using the World Health Organization (WHO) Health Systems building blocks as a framework, 20 Key-Informant Interviews were conducted to explore facilitators and barriers to routine implementation of DCC in public health settings. Existing quantitative program data and secondary data from labour-room registers from eight NI- supported districts were analysed to assess the prevalence of DCC implementation in public health systems settings. RESULTS: A demonstrated commitment from the government to implement DCC at all delivery points in NI supported districts was observed. Funds were sufficient, trainings were optimal, knowledge of the health workforce was adequate and a recording mechanism was in place. According to record reviews, DCC was more likely to happen in facilities that provide Basic Emergency Obstetric services and among normal deliveries. It was less likely to be followed in babies delivered by Caesarean section (OR 0.03; 95%CI 0.02,0.05), birthweight < 2000 g (OR 0.22; 95%CI 0.12,0.47), multiple pregnancies (OR 0.17, 95%CI 0.05,0.63), birth asphyxia requiring resuscitation (0.37; 95%CI 0.26,0.52), and those delivered during day shift (OR 0.59, 95%CI 0.40, 0.83). CONCLUSIONS: Wide coverage of DCC in public health settings in the two states was observed. Good governance, adequate funding, commitment of health workforce has likely contributed to its success in these contexts. These are critical elements to guide DCC implementation in India and for consideration in other settings.

A hybrid type I, multi-center randomized controlled trial to study the implementation of a method for Sustained cord circulation And VEntilation (the SAVE-method) of late preterm and term neonates: a study protocol.

BACKGROUND: An intact umbilical cord allows the physiological transfusion of blood from the placenta to the neonate, which reduces infant iron deficiency and is associated with improved development during early childhood. The implementation of delayed cord clamping practice varies depending on mode of delivery, as well as gestational age and neonatal compromise. Emerging evidence shows that infants requiring resuscitation would benefit if respiratory support were provided with the umbilical cord intact. Common barriers to providing intact cord resuscitation is the availability of neonatal resuscitation equipment close to the mother, organizational readiness for change as well as attitudes and beliefs about placental transfusion within the multidisciplinary team. Hence, clinical evaluations of cord clamping practice should include implementation outcomes in order to develop strategies for optimal cord management practice. METHODS: The Sustained cord circulation And Ventilation (SAVE) study is a hybrid type I randomized controlled study combining the evaluation of clinical outcomes with implementation and health service outcomes. In phase I of the study, a method for providing in-bed intact cord resuscitation was developed, in phase II of the study the intervention was adapted to be used in multiple settings. In phase III of the study, a full-scale multicenter study will be initiated with concurrent evaluation of clinical, implementation and health service outcomes. Clinical data on neonatal outcomes will be recorded at the labor and neonatal units. Implementation outcomes will be collected from electronic surveys sent to parents as well as staff and managers within the birth and neonatal units. Descriptive and comparative statistics and regression modelling will be used for analysis. Quantitative data will be supplemented by qualitative methods using a thematic analysis with an inductive approach. DISCUSSION: The SAVE study enables the safe development and evaluation of a method for intact cord resuscitation in a multicenter trial. The study identifies barriers and facilitators for intact cord resuscitation. The knowledge provided from the study will be of benefit for the development of cord clamping practice in different challenging clinical settings and provide evidence for development of clinical guidelines regarding optimal cord clamping. TRIAL REGISTRATION: Clinicaltrials.gov, NCT04070560 . Registered 28 August 2019.

Hemoglobin differences in twins are related to the time of cord clamping, not intertwin transfusion - a prospective cohort study.

BACKGROUND: Delayed cord clamping increases placental transfusion. In vaginal deliveries higher hemoglobin concentrations are found in the second-born twin. We hypothesized it is unrelated to intertwin transfusion but to the time of cord clamping. METHODS: It was a prospective cohort study of 202 women delivering twins > 32 weeks of gestation. Monoamniotic pregnancy, antenatal intertwin transfusions, fetal demise or major abnormalities were excluded from the study. The time of cord clamping depended on the obstetrician's decision. Hemoglobin, hematocrit, and reticulocyte count were measured at birth and during the second day of life. RESULTS: At birth, hemoglobin and hematocrit levels were significantly higher in the first-born twins delivered with delayed than with early cord clamping. Higher hemoglobin and hematocrit levels were observed during the second day of life in all twins delivered with delayed cord clamping. The lowest levels were observed in twins delivered with early cord clamping. Infants delivered with delayed cord clamping were at a lower risk of respiratory disorders and NICU hospitalization. CONCLUSION: The observed differences in Hgb concentrations between the infants in a twin pregnancy are related to cord clamping time.