2023 American Heart Association and American Academy of Pediatrics Focused Update on Neonatal Resuscitation: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care.

This 2023 focused update to the neonatal resuscitation guidelines is based on 4 systematic reviews recently completed under the direction of the International Liaison Committee on Resuscitation Neonatal Life Support Task Force. Systematic reviewers and content experts from this task force performed comprehensive reviews of the scientific literature on umbilical cord management in preterm, late preterm, and term newborn infants, and the optimal devices and interfaces used for administering positive-pressure ventilation during resuscitation of newborn infants. These recommendations provide new guidance on the use of intact umbilical cord milking, device selection for administering positive-pressure ventilation, and an additional primary interface for administering positive-pressure ventilation.

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.

How to improve newborn outcomes in 60 s-delay clamping the umbilical cord.

Deferred umbilical cord clamping (DCC) has been employed with wide variation in the United States over the last few decades. This practice has the potential to improve infant health and outcomes at the population health level. Education campaigns and policy interventions can promote DCC use in a safe manner.

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.

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.

Deferred Cord Clamping in Twin Pregnancies Across Canada: A National Survey of Practices.

OBJECTIVE: Guidelines recommending deferred cord clamping (DCC), delaying cord clamping for at least 30 seconds post-birth, have shown significant benefits in preterm singleton births. However, evidence supporting DCC in twins is scarce due to limited trial data, leading to practice variations. This study aims to assess current reported DCC practices for twin pregnancies in tertiary hospitals across Canada. METHODS: A web-based survey was distributed to neonatologists and obstetrician investigators associated with the Canadian Neonatal and Preterm Birth Networks operating maternity and neonatal units. RESULTS: The site response rate was 93% (28/30 sites), with 83% (25/30) for neonatologists and 56% (17/30) for obstetricians. The majority had a local protocol for twin pregnancies (obstetricians 13/17, neonatologists 21/25). While all centres practised DCC in dichorionic-diamniotic twins, a difference was noted for monochorionic-diamniotic twins, with 56% of neonatologists and 65% of obstetricians performing DCC. During cesarean delivery, most obstetricians (76.5%) placed the firstborn on the mother's thighs. Neonatologists varied in their practices, with 32% placing the baby on the mother's abdomen, 32% on the mother's thighs, and 28% holding the baby at the height of the perineum. Divergent opinions were observed regarding contraindications, including risks of postpartum hemorrhage and velamentous cord insertion. CONCLUSIONS: DCC is reported to be practised in most twin deliveries among Canadian Neonatal and Preterm Birth Network centres. However, there are wide variations in practice, especially concerning the characteristics of the twins in which DCC is performed. Future research should investigate optimal cord clamping management in twins to standardize practices and maximize benefits.

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.

Effects of timing of umbilical cord clamping for mother and newborn: a narrative review.

OBJECTIVE: This narrative review was performed to evaluate the correct timing of umbilical cord clamping for term infants. It was intended to determine any advantages or disadvantages from early or delayed cord clamping for newborns, infants or mothers. METHODS: A systematic search on two databases was conducted using the PICO pattern to define a wide search. Out of 43 trials, 12 were included in this review. Three of the included studies are meta-analyses, nine are randomized controlled trials. RESULTS: Early or delayed cord clamping was defined differently in all the included trials. However, there are many advantages from delayed cord clamping of at least > 60 s for newborns and infants up to 12 months of age. The trials showed no disadvantages for newborns or mothers from delayed cord clamping, except for a lightly increased risk of jaundice or the need for phototherapy. CONCLUSION: Delayed umbilical cord clamping for term infants should be performed. Further research is needed to improve knowledge on physiological timing of umbilical cord clamping in term infants, which also leads to the same advantages as delayed cord clamping.

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.

[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.

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.

Effect of Breathing Support in Very Preterm Infants Not Breathing During Deferred Cord Clamping: A Randomized Controlled Trial (The ABC Study).

OBJECTIVE: To determine if providing respiratory support to very preterm infants who fail to breathe regularly during deferred cord clamping (DCC) decreased red cell transfusion. STUDY DESIGN: Infants less than 31 weeks of gestation undergoing DCC who were apneic or not breathing regularly at 15 seconds underwent stratified randomization. Pale, limp, and nonresponsive infants were excluded. The standard group received gentle stimulation in a neutral position for 50 seconds; the intervention group received intermittent positive pressure ventilation via face mask and T piece from 20 to 50 seconds of age with a fractional inspired oxygen of 0.3. The primary outcome was the proportion transfused, with a secondary composite outcome of death, severe intraventricular hemorrhage, or chronic lung disease. RESULTS: Of 311 assessed infants, 113 met the inclusion criteria and were studied; 57 received the intervention and 56 standard treatment. Patient characteristics were similar. Overall, 105 infants (93%) received the intended 50 seconds DCC (54 in the intervention group and 51 in the standard group). Rates of transfusion were similar (28% vs 30% in the intervention vs control groups), as were rates of the composite outcome (46% vs 38% in the intervention vs the control arms; P = .45). CONCLUSIONS: Providing breathing support during 50 seconds of DCC in this single-center cohort seemed to be safe and feasible, but did not decrease the transfusion rates or improve outcomes. TRIAL REGISTRATION: http://www.anzctr.org.au/ACTRN12615001026516.aspx.

Bilirubin Levels in Neonates ≥35 Weeks of Gestation Receiving Delayed Cord Clamping for an Extended Time-An Observational Study.

OBJECTIVE: To describe bilirubin levels in neonates ≥350/7 gestational weeks, receiving delayed cord clamping (CC), in relation to the updated Bhutani nomogram. STUDY DESIGN: This was a retrospective, observational study based on data from medical records and local data sheets. Singleton neonates, born vaginally at a gestational age ≥350/7, and with a registered time to CC and at least one registered bilirubin, were included. We excluded neonates with positive direct antiglobulin test or hemolytic disorders. Adjusted analyses were performed using ANOVA and linear or logistic regression. RESULTS: We analyzed 558 neonates, mean gestational age (SD) 39.9 (1.3) weeks. CC was performed at a median (IQR) time of 6 (5-8) minutes. The dataset contained 1330 bilirubin measurements. Median (IQR) age at bilirubin measurement was 37 (22-54) hours. Bilirubin percentiles in neonates with CC time ≥2 minutes were similar, or lower, compared with the Bhutani nomogram between 12 and 72 hours, but with greater 95th percentile at later hours of age. Phototherapy was initiated in 13 (2.3 %) of the neonates. We found no association between time to CC and hyperbilirubinemia (ß = -0.05, P = .07). Need for phototherapy was marginally greater in neonates with shorter time to CC. CONCLUSIONS: Bilirubin levels were not correlated to time to CC. Our findings indicate that CC beyond 2 minutes can be performed without additional monitoring for jaundice.

Umbilical cord milking in nonvigorous infants: a cluster-randomized crossover trial.

BACKGROUND: Delayed cord clamping and umbilical cord milking provide placental transfusion to vigorous newborns. Delayed cord clamping in nonvigorous newborns may not be provided owing to a perceived need for immediate resuscitation. Umbilical cord milking is an alternative, as it can be performed more quickly than delayed cord clamping and may confer similar benefits. OBJECTIVE: We hypothesized that umbilical cord milking would reduce admission to the neonatal intensive care unit compared with early cord clamping in nonvigorous newborns born between 35 and 42 weeks' gestation. STUDY DESIGN: This was a pragmatic cluster-randomized crossover trial of infants born at 35 to 42 weeks' gestation in 10 medical centers in 3 countries between January 2019 and May 2021. The centers were randomized to umbilical cord milking or early cord clamping for approximately 1 year and then crossed over for an additional year or until the required number of consented subjects was reached. Waiver of consent as obtained in all centers to implement the intervention. Infants were eligible if nonvigorous at birth (poor tone, pale color, or lack of breathing in the first 15 seconds after birth) and were assigned to umbilical cord milking or early cord clamping according to their birth hospital randomization assignment. The baseline characteristics and outcomes were collected following deferred informed consent. The primary outcome was admission to the neonatal intensive care unit for predefined criteria. The main safety outcome was hypoxic-ischemic encephalopathy. Data were analyzed by the intention-to-treat concept. RESULTS: Among 16,234 screened newborns, 1780 were eligible (905 umbilical cord milking, 875 early cord clamping), and 1730 had primary outcome data for analysis (97% of eligible; 872 umbilical cord milking, 858 early cord clamping) either via informed consent (606 umbilical cord milking, 601 early cord clamping) or waiver of informed consent (266 umbilical cord milking, 257 early cord clamping). The difference in the frequency of neonatal intensive care unit admission using predefined criteria between the umbilical cord milking (23%) and early cord clamping (28%) groups did not reach statistical significance (modeled odds ratio, 0.69; 95% confidence interval, 0.41-1.14). Umbilical cord milking was associated with predefined secondary outcomes, including higher hemoglobin (modeled mean difference between umbilical cord milking and early cord clamping groups 0.68 g/dL, 95% confidence interval, 0.31-1.05), lower odds of abnormal 1-minute Apgar scores (Apgar ≤3, 30% vs 34%, crude odds ratio, 0.72; 95% confidence interval, 0.56-0.92); cardiorespiratory support at delivery (61% vs 71%, modeled odds ratio, 0.57; 95% confidence interval, 0.33-0.99), and therapeutic hypothermia (3% vs 4%, crude odds ratio, 0.57; 95% confidence interval, 0.33-0.99). Moderate-to-severe hypoxic-ischemic encephalopathy was significantly less common with umbilical cord milking (1% vs 3%, crude odds ratio, 0.48; 95% confidence interval, 0.24-0.96). No significant differences were observed for normal saline bolus, phototherapy, abnormal 5-minute Apgar scores (Apgar ≤6, 15.7% vs 18.8%, crude odds ratio, 0.81; 95% confidence interval, 0.62-1.06), or a serious adverse event composite of death before discharge. CONCLUSION: Among nonvigorous infants born at 35 to 42 weeks' gestation, umbilical cord milking did not reduce neonatal intensive care unit admission for predefined criteria. However, infants in the umbilical cord milking arm had higher hemoglobin, received less delivery room cardiorespiratory support, had a lower incidence of moderate-to-severe hypoxic-ischemic encephalopathy, and received less therapeutic hypothermia. These data may provide the first randomized controlled trial evidence that umbilical cord milking in nonvigorous infants is feasible, safe and, superior to early cord clamping.

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.