This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

To assess the impact of delayed cord clamping (DCC) for 45 seconds on hemoglobin at birth and close to discharge in very low birth weight (VLBW) infants and to compare modes of delivery in infants who received DCC.

In a retrospective study, 888 VLBW infants (≤1,500 g) who survived to discharge and received immediate cord clamping (ICC) were compared with infants who received DCC. Infants who received DCC and born via Cesarean section (C-section) were compared with those born via vaginal birth.

A total of 555 infants received ICC and 333 DCC. Only 188 out of 333 VLBW infants (56.5%) born during the DCC period received DCC. DCC was associated with higher hemoglobin at birth (15.9 vs. 14.9 g/dL, p = 0.001) and close to discharge (10.7 vs. 10.1 g/dL, p < 0.001) and reduced need for blood transfusion (39.4 vs. 54.9%, p < 0.001). In the DCC group, hemoglobin at birth and close to discharge was similar in infants born via C-section and vaginal birth.

DCC for 45 seconds increased hemoglobin at birth and close to discharge and reduced need for blood transfusion in VLBW infants. DCC for 45 seconds was equally effective for infants born by C-section and vaginal delivery. Approximately 44% of VLBW infants did not receive DCC even after implementing DCC guidelines.

· Studies to date have shown that DCC improves mortality and short- and long-term outcomes in VLBW infants.. · No consistent guidelines for the duration of DCC in preterm and term neonates.. · DCC for 45 seconds increased hemoglobin at birth and close to discharge in VLBW infants..

Delayed cord clamping (DCC) has been recently adopted in neonatal resuscitation. The immediate cardiac hemodynamic effects related to DCC more than 30 seconds was not studied. We aimed to study the effect of DCC at 120 seconds compared with 30 seconds on multiple hemodynamic variables in full-term infants using an electrical cardiometry (EC) device.

Present study is a randomized clinical trial. The study was conducted with full-term infants who were delivered at the Obstetrics and Gynecology Department in Cairo University Hospital. Sixty-eight full term infants were successfully enrolled in this trial. Cardiac output (CO) and other hemodynamic parameters were evaluated in this study by EC device. Hemoglobin, glucose, and bilirubin concentrations were measured at 24 hours. Newborn infants were assigned randomly into group 1: DCC at 30 seconds, and group 2: DCC at 120 seconds, based on the time of cord clamping.

Stroke volume (SV) (mL) and CO (L/min) were significantly higher in group 2 compared with group 1 at 5 minutes (6.71 vs. 5.35 and 1.09 vs. 0.75), 10 minutes (6.43 vs. 5.59 and 0.88 vs. 0.77), 15 minutes (6.45 vs. 5.60 and 0.89 vs. 0.76), and 24 hours (6.67 vs. 5.75 and 0.91vs. 0.81), respectively. Index of contractility (ICON; units) was significantly increased in group 2 at 5 minutes compared with group1 (114.2 vs. 83.8). Hematocrit (%) and total bilirubin concentrations (mg/dL) at 24 hours were significantly increased in group 2 compared with group 1 (51.5 vs. 40.5 and 3.8 vs. 2.9, respectively).

Stroke volume and cardiac output are significantly higher in neonates with DCC at 120 seconds compared with 30 seconds that continues for the first 24 hours.

· CO is significantly increased with DCC at 120 seconds.. · SV is significantly increased with DCC at 120 seconds.. · Such effects continued during the entire 24 hours of life in full-term infants..

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.

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.

Umbilical cord clamping strategies at preterm birth have the potential to affect important health outcomes. The aim of this study was to compare the effectiveness of deferred cord clamping, umbilical cord milking, and immediate cord clamping in reducing neonatal mortality and morbidity at preterm birth.

We conducted a systematic review and individual participant data meta-analysis. We searched medical databases and trial registries (from database inception until Feb 24, 2022; updated June 6, 2023) for randomised controlled trials comparing deferred (also known as delayed) cord clamping, cord milking, and immediate cord clamping for preterm births (<37 weeks' gestation). Quasi-randomised or cluster-randomised trials were excluded. Authors of eligible studies were invited to join the iCOMP collaboration and share individual participant data. All data were checked, harmonised, re-coded, and assessed for risk of bias following prespecified criteria. The primary outcome was death before hospital discharge. We performed intention-to-treat one-stage individual participant data meta-analyses accounting for heterogeneity to examine treatment effects overall and in prespecified subgroup analyses. Certainty of evidence was assessed with Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO, CRD42019136640.

We identified 2369 records, of which 48 randomised trials provided individual participant data and were eligible for our primary analysis. We included individual participant data on 6367 infants (3303 [55%] male, 2667 [45%] female, two intersex, and 395 missing data). Deferred cord clamping, compared with immediate cord clamping, reduced death before discharge (odds ratio [OR] 0·68 [95% CI 0·51-0·91], high-certainty evidence, 20 studies, n=3260, 232 deaths). For umbilical cord milking compared with immediate cord clamping, no clear evidence was found of a difference in death before discharge (OR 0·73 [0·44-1·20], low certainty, 18 studies, n=1561, 74 deaths). Similarly, for umbilical cord milking compared with deferred cord clamping, no clear evidence was found of a difference in death before discharge (0·95 [0·59-1·53], low certainty, 12 studies, n=1303, 93 deaths). We found no evidence of subgroup differences for the primary outcome, including by gestational age, type of delivery, multiple birth, study year, and perinatal mortality.

This study provides high-certainty evidence that deferred cord clamping, compared with immediate cord clamping, reduces death before discharge in preterm infants. This effect appears to be consistent across several participant-level and trial-level subgroups. These results will inform international treatment recommendations.

Australian National Health and Medical Research Council.

An extrauterine placental perfusion (EPP) approach for physiological-based cord clamping (PBCC) may support infants with very low birth weight (VLBW) during transition without delaying measures of support.

To test whether EPP in resuscitation of infants with VLBW results in higher hematocrit levels, better oxygenation, or improved infant outcomes compared with delayed cord clamping (DCC).

This nonblinded, single-center randomized clinical trial was conducted at a tertiary care neonatal intensive care unit. Infants with a gestational age greater than 23 weeks and birth weight less than 1500 g born by cesarean delivery between May 2019 and June 2021 were included. Data were analyzed from October through December 2021.

Prior to cesarean delivery, participants were allocated to receive EPP or DCC. In the EPP group, infant and placenta, connected by an intact umbilical cord, were detached from the uterus and transferred to the resuscitation unit. Respiratory support was initiated while holding the placenta over the infant. The umbilical cord was clamped when infants showed regular spontaneous breathing, stable heart rates greater than 100 beats/min, and adequate oxygen saturations. In the DCC group, cords were clamped 30 to 60 seconds after birth before infants were transferred to the resuscitation unit, where respiratory support was started.

The primary outcome was the mean hematocrit level in the first 24 hours after birth. Secondary prespecified outcome parameters comprised oxygenation during transition and short-term neonatal outcome.

Among 60 infants randomized and included, 1 infant was excluded after randomization; there were 29 infants in the EPP group (mean [SD] gestational age, 27 weeks 6 days [15.0 days]; 14 females [48.3%]) and 30 infants in the DCC group (mean [SD] gestational age, 28 weeks 1 day [17.1 days]; 17 females [56.7%]). The mean (SD) birth weight was 982.8 (276.6) g and 970.2 (323.0) g in the EPP and DCC group, respectively. Intention-to-treat analysis revealed no significant difference in mean hematocrit level (mean difference [MD], 2.1 percentage points; [95% CI, -2.2 to 6.4 percentage points]). During transition, infants in the EPP group had significantly higher peripheral oxygen saturation as measured by pulse oximetry (adjusted MD at 5 minutes, 15.3 percentage points [95% CI, 2.0 to 28.6 percentage points]) and regional cerebral oxygen saturation (adjusted MD at 5 minutes, 11.3 percentage points [95% CI, 2.0 to 20.6 percentage points]). Neonatal outcome parameters were similar in the 2 groups.

This study found that EPP resulted in similar hematocrit levels as DCC, with improved cerebral and peripheral oxygenation during transition. These findings suggest that EPP may be an alternative procedure for PBCC in infants with VLBW.

ClinicalTrials.gov Identifier: NCT03916159.

The Australian Placental Transfusion Study (APTS) randomised 1,634 fetuses to delayed (≥60 s) versus immediate (≤10 s) clamping of the umbilical cord. Systematic reviews with meta-analyses, including this and similar trials, show that delaying clamping in preterm infants reduces mortality and need for blood transfusions. Amongst 1,531 infants in APTS followed up at two years, aiming to delay clamping for 60 s or more reduced the relative risk of the primary composite outcome of death or disability by 17% (p = 0.01). However, this result is fragile because nominal statistical significance (p < 0.05) would be abolished by only 2 patients switching from a non-event to an event, and the primary composite outcome was missing in 112 patients (7%). To achieve more robust evidence, any future trials should emulate the large, simple trials co-ordinated from Oxford which reliably identified moderate, incremental improvements in mortality in tens of thousands of participants, with <1% missing data. Those who fund, regulate, and conduct trials that aim to change practice should repay the trust of those who consent to participate by doing everything possible to minimise missing data for key outcomes.

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.

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.

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.

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.

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.

The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) maintains a database of extremely preterm infants known as the Generic Database (GDB). Begun in 1987, this database now includes more than 91,000 infants, most of whom are extremely preterm (<29 weeks gestation). The GDB has been the backbone of the NRN, providing high quality, prospectively collected data to study the changing epidemiology of extreme prematurity and its outcomes over time. In addition, GDB data have been used to generate hypotheses for prospective studies and to develop new clinical trials by providing information about the numbers and characteristics of available subjects and the expected event rates for conditions and complications to be studied. Since its inception, the GDB has been the basis of more than 200 publications in peer-reviewed journals, many of which have had a significant impact on the field of neonatology.

Delaying umbilical cord clamping facilitates postnatal transition in neonates but evidence on its effect in reducing hemodynamic instability in preterm neonates is inconclusive.

To evaluate delayed cord clamping (DCC) in reducing the incidence of hemodynamic instability in preterm neonates below 35 weeks gestational age admitted to the neonatal intensive care unit.

Neonates between 25 weeks and 34 weeks and 6 days gestation were enrolled. Hemodynamic and respiratory parameters were monitored over 48 h. Hemodynamic instability was defined as persistent tachycardia and/or hypotension necessitating therapy.

The DCC cohort included 62 neonates with an equal number in the non-DCC group. The birth weight [mean ± standard deviation (SD)] was 1332.90 ± 390.05 g and the gestational age (mean ± SD) was 31.64 ± 2.52 weeks. Hemodynamic instability was noted in 18/62 (29%) neonates in the DCC cohort and 29/62 (46.7%) in the non-DCC group; relative risk (RR) 0.62 [95% confidence interval (CI) 0.38-0.99] (p = 0.023). The duration of inotrope requirement in the DCC cohort (mean ± SD) was 38.38 ± 16.99 h compared to 49.13 ± 22.90 h in the non-DCC cohort (p = 0.090). Significantly higher systolic, diastolic and mean arterial pressures were noted from 6 h to 48 h in the DCC cohort (p < 0.001). The severity of respiratory distress and FiO2 requirement was also less in the first 24 h. There was no difference in the incidence of patent ductus arteriosus, late-onset sepsis or mortality.

Delaying umbilical cord clamping at birth by 60 s resulted in significantly lower hemodynamic instability in the first 48 h and higher blood pressure parameters.

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.

Despite their potential benefits, placental transfusions have shown to alter the hemodynamics and adversely affect myocardial function of premature neonates.

This trial was registered in the clinical trial gov NCT04811872.

• Placental transfusion techniques might have benefits regarding prematurity- related morbidities and mortality.

• Placental transfusion might adversely affect the myocardium and alter hemodynamics in premature infants.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

The International Liaison Committee on Resuscitation initiated a continuous review of new, peer-reviewed published cardiopulmonary resuscitation science. This is the fifth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation task force science experts. Topics covered by systematic reviews in this summary include resuscitation topics of video-based dispatch systems; head-up cardiopulmonary resuscitation; early coronary angiography after return of spontaneous circulation; cardiopulmonary resuscitation in the prone patient; cord management at birth for preterm and term infants; devices for administering positive-pressure ventilation at birth; family presence during neonatal resuscitation; self-directed, digitally based basic life support education and training in adults and children; coronavirus disease 2019 infection risk to rescuers from patients in cardiac arrest; and first aid topics, including cooling with water for thermal burns, oral rehydration for exertional dehydration, pediatric tourniquet use, and methods of tick removal. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, according to the Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations or good practice statements. Insights into the deliberations of the task forces are provided in Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces listed priority knowledge gaps for further research.

To compare and evaluate the efficacy and safety of immediate cord clamping (ICC) and delayed cord clamping (DCC) in preterm infants. We performed a comprehensive and systematic meta-analysis of randomised controlled trials (RCTs) assessing ICC and DCC in preterm infants by searching PUBMED, EMBASE, Science Direct, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Database (from inception to 30 September 2020). Summary odds ratios or mean differences with 95% confidence intervals were calculated using a fixed- or random-effect model. A total of 20 RCTs with 1807 preterm infants were included in the study. DCC provided more benefits in increasing the haematocrit and haemoglobin levels at 24 hours of life (%), thus reducing the incidence of anaemia, necrotising enterocolitis, length of hospital stay and mortality than when ICC was performed. No significant differences were found between ICC and DCC in terms of peak bilirubin level; need for blood transfusion, mechanical ventilation (MV) and phototherapy; duration of MV and phototherapy; and incidences of intraventricular haemorrhage, retinopathy of prematurity, patent ductus arteriosus, respiratory distress syndrome, sepsis, jaundice, polycythaemia, periventricular leukomalacia and bronchopulmonary dysplasia. DCC is a safe, beneficial and feasible intervention for preterm infants. However, rigorously designed and large-scale RCTs are necessary to identify the role and ideal timing of DCC.

A comprehensive understanding of the factors contributing to perinatal blood pressure is vital to ensure optimal postnatal hemodynamic support. The objective of this study was to review existing literature on maternal and perinatal factors influencing blood pressure in neonates up to 3 months corrected age.

A systematic search of published literature in OVID Medline, OVID Embase and the COCHRANE library identified publications relating to maternal factors affecting blood pressure of neonates up to corrected age of 3 months. Summary data were extracted and compared (PROSPERO CRD42018092886).

Of the 3683 non-duplicate publications identified, 44 were eligible for inclusion in this review. Topics elicited were sociodemographic factors, maternal health status, medications, smoking during pregnancy, and cord management at birth. Limited data were available for each factor. Results regarding the impact of these factors on neonatal blood pressure were inconsistent across studies.

There is insufficient evidence to draw definitive conclusions regarding the impact of various maternal and perinatal factors on neonatal blood pressure. Future investigations of neonatal cardiovascular therapies should account for these factors in their study design. Similarly, studies on maternal diseases and perinatal interventions should include neonatal blood pressure as part of their primary or secondary analyses.

To assess the eligibility criteria and trial characteristics among contemporary (2010-2019) randomized clinical trials (RCTs) that included infants born extremely preterm (<28 weeks of gestation) and to evaluate whether eligibility criteria result in underrepresentation of high-risk subgroups (eg, infants born at <24 weeks of gestation).

PubMed and Scopus were searched January 1, 2010, to December 31, 2019, with no language restrictions. RCTs with mean or median gestational ages at birth of <28 weeks of gestation were included. The study followed the PRISMA guidelines; outcomes were registered prospectively. Data extraction was performed independently by multiple observers. Study quality was evaluated using a modified Jadad scale.

Among RCTs (n = 201), 32 552 infants were included. Study participant characteristics, interventions, and outcomes were highly variable. A total of 1603 eligibility criteria were identified; rationales were provided for 18.8% (n = 301) of criteria. Fifty-five RCTs (27.4%) included infants <24 weeks of gestation; 454 (1.4%) infants were identified as <24 weeks of gestation.

The present study identifies sources of variability across RCTs that included infants born extremely preterm and reinforces the critical need for consistent and transparent policies governing eligibility criteria.

It is unclear which umbilical cord management strategy is the best for preventing mortality and morbidities in preterm infants.

To systematically review and conduct a network meta-analysis comparing 4 umbilical cord management strategies for preterm infants: immediate umbilical cord clamping (ICC), delayed umbilical cord clamping (DCC), umbilical cord milking (UCM), and UCM and DCC.

PubMed, Embase, CINAHL, and Cochrane CENTRAL databases were searched from inception until September 11, 2020.

Randomized clinical trials comparing different umbilical cord management strategies for preterm infants were included.

Data were extracted for bayesian random-effects meta-analysis to estimate the relative treatment effects (odds ratios [OR] and 95% credible intervals [CrI]) and surface under the cumulative ranking curve values.

The primary outcome was predischarge mortality. The secondary outcomes were intraventricular hemorrhage, severe intraventricular hemorrhage, need for packed red blood cell transfusion, and other neonatal morbidities. Confidence in network meta-analysis software was used to assess the quality of evidence and grade outcomes.

Fifty-six studies enrolled 6852 preterm infants. Compared with ICC, DCC was associated with lower odds of mortality (22 trials, 3083 participants; 7.6% vs 5.0%; OR, 0.64; 95% CrI, 0.39-0.99), intraventricular hemorrhage (25 trials, 3316 participants; 17.8% vs 15.4%; OR, 0.73; 95% CrI, 0.54-0.97), and need for packed red blood cell transfusion (18 trials, 2904 participants; 46.9% vs 38.3%; OR, 0.48; 95% CrI, 0.32-0.66). Compared with ICC, UCM was associated with lower odds of intraventricular hemorrhage (10 trials, 645 participants; 22.5% vs 16.2%; OR, 0.58; 95% CrI, 0.38-0.84) and need for packed red blood cell transfusion (9 trials, 688 participants; 47.3% vs 32.3%; OR, 0.36; 95% CrI, 0.23-0.53), with no significant differences for other secondary outcomes. There was no significant difference between UCM and DCC for any outcome.

Compared with ICC, DCC was associated with the lower odds of mortality in preterm infants. Compared with ICC, DCC and UCM were associated with reductions in intraventricular hemorrhage and need for packed red cell transfusion. There was no significant difference between UCM and DCC for any outcome. Further studies directly comparing DCC and UCM are needed.

The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management strategies at preterm birth.

To determine the effects of umbilical cord management strategies (including timing of cord clamping and cord milking) in preterm infants <34 weeks' gestation.

Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, CINAHL, and trial registries were searched through July 2019 for randomized controlled trials assessing timing of cord clamping and/or cord milking.

Two authors independently assessed trial eligibility, extracted data, appraised risk of bias, and assessed evidence certainty (GRADE).

We identified 42 randomized controlled trials (including 5772 infants) investigating 4 different comparisons of cord management interventions.

Compared to early cord clamping, delayed cord clamping (DCC) and intact-cord milking (ICM) may slightly improve survival; however, both are compatible with no effect (DCC: risk ratio: 1.02, 95% confidence interval: 1.00 to 1.04, n = 2988 infants, moderate certainty evidence; ICM: risk ratio: 1.02, 95% confidence interval: 0.98 to 1.06, n = 945 infants, moderate certainty evidence). DCC and ICM both probably improve hematologic measures but may not affect major neonatal morbidities.

For many of the included comparisons and outcomes, certainty of evidence was low. Our subgroup analyses were limited by few researchers reporting subgroup data.

DCC appears to be associated with some benefit for infants born <34 weeks. Cord milking needs further evidence to determine potential benefits or harms. The ideal cord management strategy for preterm infants is still unknown, but early clamping may be harmful.

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

The current recommendation for umbilical cord management of non-vigorous infants (limp, pale, and not breathing) who need resuscitation at birth is to immediately clamp the umbilical cord. This recommendation is due in part to insufficient evidence for delayed cord clamping (DCC) or umbilical cord milking (UCM). These methods may provide a neuroprotective mechanism that also facilitates cardiovascular transition for non-vigorous infants at birth.

Background: Extremely low birth-weight (ELBW) preterm infants remain at high risk for mortality and major morbidities, and nearly all need packed red blood cell transfusions within their first weeks of life. The overall objective of this study was to assess the association between anemia at admission to neonatal intensive care unit (NICU) with the neonatal morbidity and mortality in ELBW infants.Methods: This retrospective study was conducted on 106 patients with ELBW admitted at our level III NICU from January 2006 to December 2015. The subjects were divided into two groups: (1) patients with anemia at admission and (2) patients without anemia. Their characteristics and outcomes were compared. Statistical analysis was performed using the Statistical Package for the Social Sciences software, version 24.0 (IBM New York, USA), and a value of p < 0.05 was considered statistically significant.Results: Of the 106 ELBW, 34 (32%) presented with anemia at admission and 72 (68%) without anemia. Anemia-naive presented mean hemoglobin at the admission of 12.8 ± 1.5 g/dl and nonanemic 16.8 ± 2.1 g/dl, p < .001). The anemic group presented a lower gestational age (26 ± 2 vs. 27 ± 2 SD weeks, p = .025), greater need for inotropic support (52.9 vs. 31.9%, p = .041), longer period of invasive mechanical ventilation (9 vs. 2 days, p = .012), higher FiO₂ need (0.8 vs. 0.4, p < .001), more frequent hemodynamically significant patent ductus arteriosus (HS-PDA) (64.7 vs. 41.7%, p = .006) and severe intra-periventricular hemorrhage (IPVH) (41.2 vs. 16.7%, p = 0.005). The multivariate analysis confirmed an association between anemia at admission and HS-PDA (OR = 3.2; 95% CI: 1.1-9.5, p = 0.044) and severe IPVH (OR = 3.3; 95% CI: 1.0-9.9, p = .038). In anemic infants, ionotropic support and IPVH >2 were considered independent factors for mortality.Conclusion: In this ELBW series, the presence of anemia at admission to the NICU was associated with HS-PDA and severe IPVH. Preventive strategies for early anemia must be encouraged.

Infants born preterm (before 37 weeks' gestation) have poorer outcomes than infants at term, particularly if born before 32 weeks. Early cord clamping has been standard practice over many years, and enables quick transfer of the infant to neonatal care. Delayed clamping allows blood flow between the placenta, umbilical cord and baby to continue, and may aid transition. Keeping baby at the mother's side enables neonatal care with the cord intact and this, along with delayed clamping, may improve outcomes. Umbilical cord milking (UCM) is proposed for increasing placental transfusion when immediate care for the preterm baby is needed. This Cochrane Review is a further update of a review first published in 2004 and updated in 2012.

To assess the effects on infants born at less than 37 weeks' gestation, and their mothers of: 1) delayed cord clamping (DCC) compared with early cord clamping (ECC) both with immediate neonatal care after cord clamping; 2) DCC with immediate neonatal care with cord intact compared with ECC with immediate neonatal care after cord clamping; 3) DCC with immediate neonatal care after cord clamping compared with UCM; 4) UCM compared with ECC with immediate neonatal care after cord clamping.

We searched the Cochrane Pregnancy and Childbirth Group Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (10 November 2017), and reference lists of retrieved studies. We updated the search in November 2018 and added nine new trial reports to the awaiting classification section to be assessed at the next update.

Randomised controlled trials (RCTs) comparing delayed with early clamping of the umbilical cord (with immediate neonatal care after cord clamping or with cord intact) and UCM for births before 37 weeks' gestation. Quasi-RCTs were excluded.

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Random-effects are used in all meta-analyses. Review authors assessed the certainty of the evidence using the GRADE approach.

This update includes forty-eight studies, involving 5721 babies and their mothers, with data available from 40 studies involving 4884 babies and their mothers. Babies were between 24 and 36+6 weeks' gestation at birth and multiple births were included. The data are mostly from high-income countries. Delayed clamping ranged between 30 to 180 seconds, with most studies delaying for 30 to 60 seconds. Early clamping was less than 30 seconds and often immediate. UCM was mostly before cord clamping but some were milked after cord clamping. We undertook subgroup analysis by gestation and type of intervention, and sensitivity analyses by low risk of selection and attrition bias.All studies were high risk for performance bias and many were unclear for other aspects of risk of bias. Certainty of the evidence using GRADE was mostly low, mainly due to imprecision and unclear risk of bias.Delayed cord clamping (DCC) versus early cord clamping (ECC) both with immediate neonatal care after cord clamping (25 studies, 3100 babies and their mothers)DCC probably reduces the number of babies who die before discharge compared with ECC (average risk ratio (aRR) 0.73, 95% confidence interval (CI) 0.54 to 0.98, 20 studies, 2680 babies (moderate certainty)).No studies reported on 'Death or neurodevelopmental impairment' in the early years'.DCC may make little or no difference to the number of babies with severe intraventricular haemorrhage (IVH grades 3 and 4) (aRR 0.94, 95% CI 0.63 to 1.39, 10 studies, 2058 babies, low certainty) but slightly reduces the number of babies with any grade IVH (aRR 0.83, 95% CI 0.70 to 0.99, 15 studies, 2333 babies, high certainty).DCC has little or no effect on chronic lung disease (CLD) (aRR 1.04, 95% CI 0.94 to 1.14, 6 studies, 1644 babies, high certainty).Due to insufficient data, we were unable to form conclusions regarding periventricular leukomalacia (PVL) (aRR 0.58, 95% CI 0.26 to 1.30, 4 studies, 1544 babies, low certainty) or maternal blood loss of 500 mL or greater (aRR 1.14, 95% CI 0.07 to 17.63, 2 studies, 180 women, very low certainty).We identified no important heterogeneity in subgroup or sensitivity analyses.Delayed cord clamping (DCC) with immediate neonatal care with cord intact versus early cord clamping (ECC) (one study, 276 babies and their mothers)There are insufficient data to be confident in our findings, but DCC with immediate neonatal care with cord intact may reduce the number of babies who die before discharge, although the data are also compatible with a slight increase in mortality, compared with ECC (aRR 0.47, 95% CI 0.20 to 1.11, 1 study, 270 babies, low certainty). DCC may also reduce the number of babies who die or have neurodevelopmental impairment in early years (aRR 0.61, 95% CI 0.39 to 0.96, 1 study, 218 babies, low certainty). There may be little or no difference in: severe IVH; all grades IVH; PVL; CLD; maternal blood loss ≥ 500 mL, assessed as low certainty mainly due to serious imprecision.Delayed cord clamping (DCC) with immediate neonatal care after cord clamping versus umbilical cord milking (UCM) (three studies, 322 babies and their mothers) and UCM versus early cord clamping (ECC) (11 studies, 1183 babies and their mothers)There are insufficient data for reliable conclusions about the comparative effects of UCM compared with delayed or early clamping (mostly low or very low certainty).

Delayed, rather than early, cord clamping may reduce the risk of death before discharge for babies born preterm. There is insufficient evidence to show what duration of delay is best, one or several minutes, and therefore the optimum time to clamp the umbilical cord remains unclear. Whilst the current evidence supports not clamping the cord before 30 seconds at preterm births, future trials could compare different lengths of delay. Immediate neonatal care with the cord intact requires further study, and there are insufficient data on UCM.The nine new reports awaiting further classification may alter the conclusions of the review once assessed.

Delayed cord clamping (DCC) improves neurologic outcomes in preterm infants through a reduction in intraventricular hemorrhage (IVH) incidence. The mechanism behind this neuroprotective effect is not known. Infants born <28 wk gestation were recruited for longitudinal monitoring. All infants underwent 72 h of synchronized near-infrared spectroscopy (NIRS) and mean arterial blood pressure (MABP) recording within 24 h of birth. Infants with DCC were compared with control infants with immediate cord clamping (ICC), controlling for severity of illness [clinical risk index for babies (CRIB-II) score], chorioamnionitis, antenatal steroids, sedation, inotropes, and delivery mode. Autoregulatory dampening was calculated as the transfer function gain coefficient between the MABP and NIRS signals. Forty-five infants were included (DCC; n = 15, paired 2:1 with ICC controls n = 30). ICC and DCC groups were similar including gestational age (25.5 vs. 25.2 wk, P = 0.48), birth weight (852.3 vs. 816.6 g, P = 0.73), percent female (40 vs. 40%, P = 0.75), and dopamine usage (27 vs. 23%, P = 1.00). There was a significant difference in IVH incidence between the DCC and ICC groups (20 vs. 50%, P = 0.04). Mean MABP was not different (35.9 vs. 35.1 mmHg, P = 0.44). Compared with the DCC group, the ICC group had diminished autoregulatory dampening capacity (-12.96 vs. -15.06 dB, P = 0.01), which remained significant when controlling for confounders. Dampening capacity was, in turn, strongly associated with decreased risk of IVH (odds ratio = 0.14, P < 0.01). The results of this pilot study demonstrate that DCC is associated with improved dynamic cerebral autoregulatory function and may be the mechanism behind the decreased incidence of IVH. NEW & NOTEWORTHY The neuroprotective mechanism of delayed cord clamping in premature infants is unclear. Delayed cord clamping was associated with improved cerebral autoregulatory function and a marked decrease in intraventricular hemorrhage (IVH). Improved dynamic cerebral autoregulation may decrease arterial baroreceptor sensitivity, thereby reducing the risk of IVH.

Deferred cord clamping (DCC) is recommended for term and preterm neonates to reduce neonatal complications. Information on the association of DCC with outcomes for extremely low-gestational-age neonates is limited.

To compare neonatal outcomes after DCC and immediate cord clamping (ICC) in extremely low-gestational-age neonates.

In this retrospective cohort study, eligible neonates born between January 1, 2011, and December 31, 2015, were divided into 2 groups: DCC and ICC. Neonates were recruited from tertiary neonatal intensive care units participating in the Canadian Neonatal Network, and analysis began in January 2018. Neonates were eligible if they were born at 22 to 28 weeks' gestational age and admitted to a participating Canadian Neonatal Network neonatal intensive care unit during the study period. Neonates who were born outside a tertiary-level neonatal intensive care unit, were moribund at birth, needed palliative care before delivery, had major congenital anomalies, or lacked cord clamping information were excluded.

Composite of severe neurological injury (intraventricular hemorrhage grade ≥3 with or without persistent periventricular echogenicity) or mortality before discharge.

Of 8221 admitted neonates, 4680 were included in the study, of whom 1852 (39.6%) received DCC and 2828 (60.4%) received ICC. There were 974 (52.7%) male neonates in the DCC group and 1540 (54.5%) male neonates in the ICC group. Median (interquartile range) gestational age was 27 (25-28) weeks for the DCC group and 26 (25-27) weeks for the ICC group. Median (interquartile range) birth weight was 930 (760-1120) g and 870 (700-1060) g for DCC and ICC groups, respectively. Neonates who received DCC had significantly reduced odds of the composite outcome of severe neurological injury or mortality (adjusted odds ratio [AOR], 0.80; 95% CI, 0.67-0.96), mortality (AOR, 0.74; 95% CI, 0.59-0.93), and severe neurological injury (AOR, 0.80; 95% CI, 0.64-0.99). The odds of bronchopulmonary dysplasia (AOR, 1.00; 95% CI, 0.84-1.19), retinopathy of prematurity stage 3 or higher (AOR, 0.94; 95% CI, 0.71-1.25), necrotizing enterocolitis stage 2 or higher (AOR, 0.86; 95% CI, 0.66-1.12), late-onset sepsis (AOR, 1.02; 95% CI, 0.85-1.22), and receipt of 2 or more blood transfusions (AOR, 0.93; 95% CI, 0.79-1.10) did not differ between the groups. Propensity score-matched analyses revealed lower odds of mortality (AOR, 0.79; 95% CI, 0.65-0.95), late-onset sepsis (AOR, 0.81; 95% CI, 0.69-0.95), and treatment for hypotension (AOR, 0.75; 95% CI, 0.60-0.95) in the DCC group.

In this study of extremely low-gestational-age neonates who received DCC or ICC, DCC was associated with reduced risk for the composite outcome of severe neurological injury or mortality.

Our specific, measurable, attainable, relevant, and time-limited (SMART) aim was to reduce the incidence of severe intracranial hemorrhage (ICH) among preterm infants born <30 weeks' gestation from a baseline of 24% (January 2012-December 2013) to a long-term average of 11% by December 2015.

We instituted an ICH bundle consisting of elements of the "golden hour" (delayed cord clamping, optimized cardiopulmonary resuscitation, improved thermoregulation) and provision of cluster care in the neonatal intensive care unit (NICU). We identified key drivers to achieve our SMART aims, and implemented quality improvement (QI) cycles: initiation of the ICH bundle, education of NICU staff, and emphasis on sustained adherence. We excluded infants born outside our facility and those with congenital anomalies.

Using statistical process control analysis (p-chart), the ICH bundle was associated with successful reduction in severe ICH (grade 3-4) in our NICU from a prebundle rate of 24% (January 2012-December 2013) to a sustained reduction over the next 4 years to an average rate of 9.7% by December 2017. Results during 2016-2017 showed a sustained improvement beyond the goal for 2014-2015. Over the same interval, there was improvement in admission temperatures [median 36.1 °C (interquartile range: 35.3-36.7 °C) vs. 37.1 °C (36.8-37.5 °C), p < 0.01] and a decrease in mortality rate [pre: 16/117 (14%) vs. post: 16/281 (6%), P < 0.01].

Our multidisciplinary QI initiative decreased severe ICH in our institution from a baseline rate of 24% to a lower rate of 9.7% over the ensuing 4 years. Intensive focus on sustained implementation of an ICH bundle protocol consisting of improved delivery room management, thermoregulation, and clustered care in the NICU was temporally associated with a clinically significant reduction in severe ICH.

Advances made in the last several decades in the care of the fetus and newborn have had a significant impact on morbidity and mortality. Delayed umbilical cord clamping in the preterm newborn results in fewer transfusions for anemia, decreased intraventricular hemorrhage, and decreased necrotizing enterocolitis. Because of advances made in fetal ultrasound diagnosis and technological advances, fetal surgeries to treat congenital diaphragmatic hernia, myelomeningocele, twin-to-twin transfusion syndrome, fetal lower urinary tract obstructions, amniotic band syndrome, and congenital cystic adenoid malformation or congenital pulmonary airway malformations have improved the quality of life and survival for these patients.

To adopt evidence-based recommendations to delay cord clamping in vigorous preterm neonates.

Evidence-based practice change project with quantitative data.

Delayed cord clamping (DCC) was not a usual practice at the hospital where this project took place, despite research findings that show benefits of DCC for preterm neonates.

Vigorous neonates born before 37 weeks completed gestation.

An interprofessional obstetric team of obstetricians and registered nurses implemented DCC for up to 1 minute for vigorous preterm neonates.

We found that Apgar scores at 1 minute (mean [M] = 8.35, standard deviation [SD] = .551, n = 31) were statistically significantly higher with DCC than at 1 minute with immediate cord clamping (M = 7.16, SD = 1.834, n = 19) at t (20.008) = 1.197, p = .012. The Apgar scores at 5 minutes (M = 9.00, SD = 0.258, n = 31) were statistically significantly higher with DCC than at 5 minutes with immediate cord clamping (M = 8.58, SD = .838, n = 19) at t (20.116) = 2.130, p = 0.046.

Delayed cord clamping was adopted as a usual clinical practice, and implementation of this practice in vigorous preterm neonates increased their Apgar scores. The obstetric team's awareness, experience, and professional perspectives about DCC improved.

Over five percent of infants born worldwide will need help breathing after birth. Delayed cord clamping (DCC) has become the standard of care for vigorous infants. DCC in non-vigorous infants is uncommon because of logistical difficulties in providing effective resuscitation during DCC. In Baby-Directed Umbilical Cord Clamping (Baby-DUCC), the umbilical cord remains patent until the infant's lungs are exchanging gases. We conducted a feasibility study of the Baby-DUCC technique.

We obtained antenatal consent from pregnant women to enroll infants born at ≥32 weeks. Vigorous infants received ≥2 min of DCC. If the infant received respiratory support, the umbilical cord was clamped ≥60 s after the colorimetric carbon dioxide detector turned yellow. Maternal uterotonic medication was administered after umbilical cord clamping. A paediatrician and researcher entered the sterile field to provide respiratory support during a cesarean birth. Maternal and infant outcomes in the delivery room and prior to hospital discharge were analysed.

Forty-four infants were enrolled, 23 delivered via cesarean section (8 unplanned) and 15 delivered vaginally (6 via instrumentation). Twelve infants were non-vigorous. ECG was the preferred method for recording HR. Two infants had a HR < 100 BPM. All HR values were >100 BPM by 80 s after birth. Median time to umbilical cord clamping was 150 and 138 s in vigorous and non-vigorous infants, respectively. Median maternal blood loss was 300 ml.

It is feasible to provide resuscitation to term and near-term infants during DCC, after both vaginal and cesarean births, clamping the umbilical cord only when the infant is physiologically ready.

Placental transfusion (by means of delayed cord clamping (DCC), cord milking, or cord stripping) confers benefits for preterm infants. It is not known if providing respiratory support to preterm infants before cord clamping improves outcomes.

To assess the efficacy and safety of respiratory support provided during DCC compared with no respiratory support during placental transfusion (in the form of DCC, milking, or stripping) in preterm infants immediately after delivery.

We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL, 2017, Issue 5), MEDLINE via PubMed (1966 to 19 June 2017), Embase (1980 to 19 June 2017), and CINAHL (1982 to 19 June 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials and quasi-randomized trials.

Randomized, cluster randomized, or quasi-randomized controlled trials enrolling preterm infants undergoing DCC, where one of the groups received respiratory support before cord clamping and the control group received no respiratory support before cord clamping.

All review authors assisted with data collection, assessment, and extraction. Two review authors assessed the quality of evidence using the GRADE approach. We contacted study authors to request missing information.

One study fulfilled the review criteria. In this study, 150 preterm infants of less than 32 weeks' gestation undergoing 60 second DCC were randomized to a group who received respiratory support in the form of continuous positive airway pressure (CPAP) or positive pressure ventilation during DCC and a group that did not receive respiratory support during the procedure. Mortality during hospital admission was not significantly different between groups with wide confidence intervals (CI) for magnitude of effect (risk ratio (RR) 1.67, 95% CI 0.41 to 6.73). The study did not report neurodevelopmental disability and death or disability at two to three years of age. There were no significant differences between groups in condition at birth (Apgar scores or intubation in the delivery room), use of inotropic agents (RR 1.25, CI 0.63 to 2.49), and receipt of blood transfusion (RR 1.03, 95% CI 0.70 to 1.54). In addition, there were no significant differences in the incidences of any intraventricular haemorrhage (RR 1.50, 95% CI 0.65 to 3.46) and severe intraventricular haemorrhage (RR 1.33, 95% CI 0.31 to 5.75). Several continuous variables were reported in subgroups depending on method of delivery. Unpublished data for each group as a whole was made available and showed peak haematocrit in the first 24 hours and duration of phototherapy did not differ significantly. Overall, the quality of evidence for several key neonatal outcomes (e.g. mortality and intraventricular haemorrhage) was low because of lack of precision with wide CIs.

The results from one study with wide CIs for magnitude of effect do not provide evidence either for or against the use of respiratory support before clamping the umbilical cord. A greater body of evidence is required as many of the outcomes of interest to the review occurred infrequently. Similarly, the one included study cannot answer the question of whether the intervention is or is not harmful.

Postnatal adaptation in preterm newborn comprises complex physiological processes that involve significant changes in the circulatory and respiratory system. Increasing hemoglobin level and blood volume following placental transfusion may be of importance in enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. The European consensus on resuscitation of preterm infants recommends delayed cord clamping (DCC) for at least 60 s to promote placenta-fetal transfusion in uncompromised neonates. Recently, published meta-analyses suggest that DCC is associated with fewer infants requiring transfusions for anemia, a lower incidence of intraventricular hemorrhage, and lower risk for necrotizing enterocolitis. Umbilical cord milking (UCM) has the potential to avoid some disadvantages associated with DCC including the increased risk of hypothermia or delay in commencing manual ventilation. UCM represents an active form of blood transfer from placenta to neonate and may have some advantages over DCC. Moreover, both methods are associated with improvement in hemodynamic parameters and blood pressure within first hours after delivery compared to immediate cord clamping. Placental transfusion appears to be beneficial for the preterm uncompromised infant. Further studies are needed to evaluate simultaneous placental transfusion with resuscitation of deteriorating neonates. It would be of great interest for future research to investigate advantages of this approach further and to assess its impact on neonatal outcomes, particularly in extremely preterm infants.

At delivery, if the cord is not clamped, blood continues to pass from the placenta to the newborn during the first minutes of life, allowing the transfer of 25-35 ml/kg of placental blood to the newborn, depending on gestational age, the timing of cord clamping, the position of the infant at birth, the onset of respiration, and administration of uterotonics to the mother. However, deriving benefits from delayed cord clamping (DCC) are not merely related to placental-to-fetal blood transfusion; establishing spontaneous ventilation before cutting the cord improves venous return to the right heart and pulmonary blood flow, protecting the newborn from the transient low cardiac output, and systemic arterial pressure fluctuations. Recent meta-analyses showed that delayed cord clamping reduces mortality and red blood cell transfusions in preterm newborns and increases iron stores in term newborns. Various authors suggested umbilical cord milking (UCM) as a safe alternative when delayed cord clamping is not feasible. Many scientific societies recommend waiting 30-60 s before clamping the cord for both term and preterm newborns not requiring resuscitation. To improve the uptake of placental transfusion strategies, in 2016 an Italian Task Force for the Management of Umbilical Cord Clamping drafted national recommendations for the management of cord clamping in term and preterm deliveries. The task force performed a detailed review of the literature using the GRADE methodological approach. The document analyzed all clinical scenarios that operators could deal with in the delivery room, including cord blood gas analysis during delayed cord clamping and time to cord clamping in the case of umbilical cord blood banking. The panel intended to promote a more physiological and individualized approach to cord clamping, specifically for the most preterm newborn. A feasible option to implement delayed cord clamping in very preterm deliveries is to move the neonatologist to the mother's bedside to assess the newborn's clinical condition at birth. This option could safely guarantee the first steps of stabilization before clamping the cord and allow DCC in the first 30 s of life, without delaying resuscitation. Contra-indications to placental transfusion strategies are clinical situations that may endanger mother 's health and those that may delay immediate newborn's resuscitation when required.

The effects of delayed cord clamping of the umbilical cord in preterm infants are unclear.

We sought to compare the effects of delayed vs early cord clamping on hospital mortality (primary outcome) and morbidity in preterm infants using Cochrane Collaboration neonatal review group methodology.

We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Chinese articles, cross-referencing citations, expert informants, and trial registries to July 31, 2017, for randomized controlled trials of delayed (≥30 seconds) vs early (<30 seconds) clamping in infants born <37 weeks' gestation. Before searching the literature, we specified that trials estimated to have cord milking in >20% of infants in any arm would be ineligible. Two reviewers independently selected studies, assessed bias, and extracted data. Relative risk (ie, risk ratio), risk difference, and mean difference with 95% confidence intervals were assessed by fixed effects models, heterogeneity by I² statistics, and the quality of evidence by Grading of Recommendations, Assessment, Development, and Evaluations.

Eighteen randomized controlled trials compared delayed vs early clamping in 2834 infants. Most infants allocated to have delayed clamping were assigned a delay of ≥60 seconds. Delayed clamping reduced hospital mortality (risk ratio, 0.68; 95% confidence interval, 0.52-0.90; risk difference, -0.03; 95% confidence interval, -0.05 to -0.01; P = .005; number needed to benefit, 33; 95% confidence interval, 20-100; Grading of Recommendations, Assessment, Development, and Evaluations = high, with I² = 0 indicating no heterogeneity). In 3 trials in 996 infants ≤28 weeks' gestation, delayed clamping reduced hospital mortality (risk ratio, 0.70; 95% confidence interval, 0.51-0.95; risk difference, -0.05; 95% confidence interval, -0.09 to -0.01; P = .02, number needed to benefit, 20; 95% confidence interval, 11-100; I² = 0). In subgroup analyses, delayed clamping reduced the incidence of low Apgar score at 1 minute, but not at 5 minutes, and did not reduce the incidence of intubation for resuscitation, admission temperature, mechanical ventilation, intraventricular hemorrhage, brain injury, chronic lung disease, patent ductus arteriosus, necrotizing enterocolitis, late onset sepsis or retinopathy of prematurity. Delayed clamping increased peak hematocrit by 2.73 percentage points (95% confidence interval, 1.94-3.52; P < .00001) and reduced the proportion of infants having blood transfusion by 10% (95% confidence interval, 6-13%; P < .00001). Potential harms of delayed clamping included polycythemia and hyperbilirubinemia.

This systematic review provides high-quality evidence that delayed clamping reduced hospital mortality, which supports current guidelines recommending delayed clamping in preterm infants. This review does not evaluate cord milking, which may also be of benefit. Analyses of individual patient data in these and other randomized controlled trials will be critically important in reliably evaluating important secondary outcomes.

Necrotizing enterocolitis (NEC) is one of the leading causes of neonatal mortality and morbidity particularly in very-low-birth-weight (VLBW) neonates. The incidence of NEC varies across countries and neonatal centers in between 7% and 14%.

The aim of this study is to evaluate the role of delayed cord clamping (DCC) for prevention of NEC in preterm neonates.

The literature search was done for various randomized control trial (RCT) by searching the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, ongoing clinical trials, and abstract of conferences.

This review included six RCTs that fulfilled inclusion criteria. There was statistically significant reduction in the incidence of NEC in DCC group (12.2% versus 20.6%; risk ratio (RR) 0.59; 95% CI 0.37-0.94; p = .02; number needed to treat (NNT) 12). However, mortality due to any cause before hospital discharge was not statistically significant (RR 0.80; 95% CI 0.33-2.00; p = .64).

The role of DCC in the prevention of NEC is supported by the current evidences. However, given the small sample sizes and other limitations of these studies, current evidences are not sufficient. We need large high-quality trials, with sufficient power to reliably assess clinically relevant differences in important outcomes.

Over the past decade, there have been several studies and reviews on the importance of providing a placental transfusion to the newborn. Allowing a placental transfusion to occur by delaying the clamping of the umbilical cord is an extremely effective method of enhancing arterial oxygen content, increasing cardiac output, and improving oxygen delivery. However, premature and term newborns who require resuscitation have impaired transitional hemodynamics and may warrant different methods to actively provide a placental transfusion while still allowing for resuscitation. In this review, we will provide evidence for providing a placental transfusion in these circumstances and methods for implementation. Several factors including cord clamping time, uterine contractions, umbilical blood flow, respirations, and gravity play an important role in determining placental transfusion volumes. Finally, while many practitioners agree that a placental transfusion is beneficial, it is not always straightforward to implement and can be performed using different methods, making this basic procedure important to discuss. We will review three placental transfusion techniques: delayed cord clamping, intact umbilical cord milking, and cut-umbilical cord milking. We will also review resuscitation with an intact cord and the evidence in term and preterm newborns supporting this practice. We will discuss perceived risks versus benefits of these procedures. Finally, we will provide key straightforward concepts and implementation strategies to ensure that placental-to-newborn transfusion can become routine practice at any institution.

To evaluate the benefit/risk balance of way of birth according to fetal presentation, to assess monitoring during preterm labor, to discuss method of delivery and practice of delayed cord clamping in case of spontaneous preterm birth.

Bibliographic research from the Pubmed database and recommendations issued by the main scientific societies, and assignment of a level of evidence and a recommendation grade.

In case of vertex presentation, no studies suggest that cesarean section improve neonatal outcome during spontaneous preterm birth (LE4). Nevertheless, cesarean is associated with higher maternal morbidity than vaginal delivery. Thus, routine cesarean is not recommended simply because of a spontaneous preterm labor (professional consensus). The available data do not allow specific recommendations about the choice of mode of delivery for preterm breech presentation in view of the low levels of proof (Professional consensus). Fetal rate monitoring is necessary during preterm labor (Professional consensus). Current data about second lines method for fetal surveillance (fetal scalp blood for pH or lactates) are insufficient to recommend their use before 34 WG (Professional consensus). Systematic assisted vaginal delivery is not recommended during preterm birth (Professional consensus). Use of vacuum is possible after 34 WG when cranial vertex ossification is considered satisfactory (Professional consensus). Systematic use of episiotomy in case of preterm birth is not recommended (Professional consensus). A delayed cord clamping is possible if the neonatal or maternal state so permits (Professional consensus). The available data are insufficient to recommend a systematic use of this procedure (LE3).

In case of preterm delivery, the available data do not allow specific recommendations about the choice of mode of delivery regardless of fetal presentation.

To investigate the influence of delayed cord clamping (DCC) on preterm infants with a gestational age of <32 weeks.

Ninety preterm infants with a gestational age of <32 weeks delivered naturally from January to December, 2015 were enrolled and randomly divided into DCC group (46 infants) and immediate cord clamping (ICC) group (44 infants). The routine blood test results, total amount of red blood cell transfusion, blood gas parameters, mean arterial pressure, bilirubin peak, total time of phototherapy, and incidence rates of necrotizing enterocolitis, late-onset sepsis, intracranial hemorrhage, retinopathy, and bronchopulmonary dysplasia were compared between the two groups.

Compared with the ICC group, the DCC group had significantly higher levels of hemoglobin, hematocrit, mean arterial pressure, and standard base excess (P<0.05), as well as a significantly lower percentage of preterm infants who underwent volume expansion and dopamine treatment and a significantly lower amount of red blood cell transfusion (P<0.05). The body temperature, pH value, HCO3(-) concentration, serum bilirubin peak, total time of phototherapy, and incidence rates of late-onset sepsis, retinopathy, grade≥2 intracranial hemorrhage, and grade≥2 neonatal necrotizing enterocolitis showed no significant differences between the two groups (P>0.05).

DCC is a safe clinical intervention and can improve the prognosis of preterm infants with a gestational age of <32 weeks.

To investigate the influence of delayed cord clamping (DCC) on preterm infants with a gestational age of <32 weeks.

Ninety preterm infants with a gestational age of <32 weeks delivered naturally from January to December, 2015 were enrolled and randomly divided into DCC group (46 infants) and immediate cord clamping (ICC) group (44 infants). The routine blood test results, total amount of red blood cell transfusion, blood gas parameters, mean arterial pressure, bilirubin peak, total time of phototherapy, and incidence rates of necrotizing enterocolitis, late-onset sepsis, intracranial hemorrhage, retinopathy, and bronchopulmonary dysplasia were compared between the two groups.

Compared with the ICC group, the DCC group had significantly higher levels of hemoglobin, hematocrit, mean arterial pressure, and standard base excess (P<0.05), as well as a significantly lower percentage of preterm infants who underwent volume expansion and dopamine treatment and a significantly lower amount of red blood cell transfusion (P<0.05). The body temperature, pH value, HCO3(-) concentration, serum bilirubin peak, total time of phototherapy, and incidence rates of late-onset sepsis, retinopathy, grade≥2 intracranial hemorrhage, and grade≥2 neonatal necrotizing enterocolitis showed no significant differences between the two groups (P>0.05).

DCC is a safe clinical intervention and can improve the prognosis of preterm infants with a gestational age of <32 weeks.

Despite significant advances in perinatal medicine, the management of extremely preterm infants in the delivery room remains a challenge. There is an increasing evidence for improved outcomes regarding the resuscitation and stabilisation of extremely preterm infants but there is a lack of evidence in the periviable (gestational age 23-25 wk) preterm subgroup. Presence of an experienced team during the delivery of extremely preterm infant to improve outcome is reviewed. Adaptation from foetal to neonatal cardiorespiratory haemodynamics is dependent on establishing an optimal functional residual capacity in the extremely preterm infants, thus enabling adequate gas exchange. There is sufficient evidence for a gentle approach to stabilisation of these fragile infants in the delivery room. Evidence for antenatal steroids especially in the periviable infants, delayed cord clamping, strategies to establish optimal functional residual capacity, importance of temperature control and oxygenation in delivery room in extremely premature infants is reviewed in this article.

Red blood cell (RBC) transfusions in very-low-birth-weight (VLBW) infants, while common, carry risk. Our objective was to determine clinical predictors of and trends in RBC transfusions among VLBW infants.

RBC transfusion practice and its clinical predictors in 1,750 VLBW (≤1,500 g) infants were analyzed in a single-center cohort across sequential epochs: 2000-2004 (Epoch 1), 2005-2009 (Epoch 2), and 2010-2013 (Epoch 3).

Overall, 1,168 (67%) infants received ≥1 transfusions. The adjusted likelihood of ≥1 transfusions decreased for each 1-g/dl increment in initial hemoglobin concentration following birth, for females, and for each 100-g increment in birth weight. The adjusted likelihood of ≥1 transfusions increased with infants receiving mechanical ventilation, with increasing length of hospital stay, necrotizing enterocolitis, and nonlethal congenital anomalies requiring surgery. The adjusted mean (SEM) number of transfusions per patient was decreased in Epoch 3, compared with Epoch 1 and Epoch 2. For an initial hemoglobin of ≥16.5 g/dl, the predicted probability of being transfused was ≤50%.

Adjusted RBC transfusions declined and female sex conferred an unexplained protection over the study period. Modest increases in initial hemoglobin by placentofetal transfusion at delivery may reduce the need for RBC transfusion.

To investigate the safety, feasibility and efficacy of delayed cord clamping (DCC) compared with immediate cord clamping (ICC) at delivery among infants born at 22 to 27 weeks' gestation.

This was a pilot, randomized, controlled trial in which women in labor with singleton pregnancies at 22 to 27 weeks' gestation were randomly assigned to ICC (cord clamped at 5 to 10 s) or DCC (30 to 45 s).

Forty mother-infant pairs were randomized. Infants in the ICC and DCC groups had mean gestational ages (GA) of 24.6 and 24.4 weeks, respectively. No differences were observed between the groups across all available safety measures, although infants in the DCC group had higher admission temperatures than infants in the ICC group (97.4 vs. 96.2 °F, P=0.04). During the first 24 h of life, blood pressures were lower in the ICC group than in the DCC group (P<0.05), despite a threefold greater incidence of treatment for hypotension (45% vs. 12%, P<0.01). Infants in the ICC group had increased numbers of red blood transfusions (in first 28 days of life) than infants in DCC group (4.1±3.9 vs. 2.8±2.2, P=0.04).

Among infants born at an average GA of 24 weeks', DCC appears safe, logistically feasible, and offers hematological and circulatory advantages compared with ICC. A more comprehensive appraisal of this practice is needed.

This systematic review evaluates the effectiveness of delayed cord clamping in preterm infants on reducing postdelivery complications of anemia, hemodynamic instability, and the development of intraventricular hemorrhages. Interventions included varying durations of delayed cord clamping with and without cord milking as compared with immediate cord clamping, shorter delays in cord clamping, and delayed cord clamping without cord milking. A comprehensive search of randomized controlled trials, observational, cohort, and before-after studies was conducted between 1946 and 2015 in the electronic databases of Ovid MEDLINE, Embase, and Google Scholar. Studies were critically appraised using the Critical Appraisal Skills Program guidelines. Twenty-seven studies were included in the review from 1997 to 2015 from varying countries. Outcome measures included hematocrit/hemoglobin levels, measured or calculated blood volumes levels, number and volume of blood transfusions, presence of hypotension and need for treatment, and development of intraventricular hemorrhage. Delayed cord clamping can lead to improved outcomes measures in preterm infants. This review supports the current recommendation to perform delayed cord clamping during preterm deliveries.