Delayed cord clamping with and without cord stripping: a prospective randomized trial of preterm neonates

doi:10.1016/j.ajog.2014.12.017

American Journal of Obstetrics and Gynecology

Volume 212, Issue 3, March 2015, Pages 394.e1-394.e5

Presented in oral format at the 81st annual meeting of the Central Association of Obstetricians and Gynecologists, Albuquerque, NM, Oct. 8-11, 2014.

https://doi.org/10.1016/j.ajog.2014.12.017 Get rights and content

Objective

Autologous blood transfusion from the placenta to the neonate at birth has been proven beneficial. Transfusion can be accomplished by either delayed cord clamping or cord stripping. Both are equally effective in previous randomized trials. We hypothesized that combining these 2 techniques would further improve outcomes in preterm neonates.

Study Design

This was a prospective randomized trial for singleton deliveries with estimated gestational ages between 22 and 31 6/7 weeks. The control protocol required a 30-second delayed cord clamping, whereas the test protocol instructed a concurrent cord stripping during the delay. The primary outcome was initial fetal hematocrit. We also examined secondary outcomes of neonatal mortality, length of time on the ventilator, days to discharge, peak bilirubin, number of phototherapy days, and neonatal complication rates.

Results

Of the 67 patients analyzed, 32 were randomized to the control arm and 35 were randomized to the test arm. The gestational ages and fetal weights were similar between the arms. Mean hematocrit of the control arm was 47.75%, and the mean hematocrit for the test arm was 47.71% (P = .98). These results were stratified by gestational age, revealing the infants less than 28 weeks had an average hematocrit of 41.2% in the control arm and 44.7% in the test arm (P = .12). In the infants with gestational ages of 28 weeks or longer, the control arm had an average hematocrit of 52.9%, which was higher than the test arm, which averaged 49.5% (P = .04). The control arm received an average of 1.53 blood transfusions, whereas the test arm received 0.97 (P = .33). The control arm had 3 neonatal deaths, and the test arm had none (P = .10). The average number of days until discharge was 71.2 for the control arm and 67.8 for the test arm (P = .66). The average number of days on the ventilator was 4.86 for the control arm and 3.06 for the test arm (P = .34).

Conclusion

Adding cord stripping to the delayed cord clamp does not result in an increased hematocrit. Data suggest trends in lower mortality and higher hematocrit in neonates born less than 28 weeks, but these were not statistically significant.

Section snippets

Materials and Methods

This was an institutional review board–approved, prospective, randomized trial performed at the University of South Alabama Children’s and Women’s Hospital between the dates of August 2012 and November 2013.

When endeavoring a study of neonatal outcomes, it would be ideal to use long-term outcomes of morbidity and mortality as primary variables; however, the sample size required to power these analyses is a difficult task in a prospective randomized control trial; therefore, previous studies

Results

During the 15 month period of the study, 70 patients were randomized. Three patients were randomized but on final review did not meet inclusion criteria and were excluded from analysis. For the 32 patients in the control arm, receiving 30 second delayed cord clamping alone, and the 35 in the test arm, receiving 30-second delayed cord clamping plus cord stripping, birthweights and gestational ages were similar (Table). The mean birthweights were 1087 g and 1111 g, and the mean gestational ages

Comment

Numerous studies have demonstrated the benefit of delayed cord clamping for preterm neonates at less than 32 weeks’ gestation.1, 5, 6, 7 If we could find a way to further utilize the placenta as a reservoir for blood, in addition to delayed cord clamping, we possibly could see an even greater benefit. An additive beneficial effect of combining delayed cord clamping and cord stripping has been speculated, but this study leads us to conclude that an increase in hematocrit over delayed cord

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Cited by (21)

2021 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Neonatal Life Support; Education, Implementation, and Teams; First Aid Task Forces; and the COVID-19 Working Group
2021, Resuscitation
Citation Excerpt :
The SysRev identified 7 trials (1073 infants) for this comparison.196,224–229 For the critical outcome of survival to discharge, moderate-certainty evidence from 5 trials involving 1000 infants could not exclude benefit or harm from later cord clamping.224–226,228,229 For all other outcomes evaluated, results were similarly inconclusive.
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.
A Comparison of Strategies for Managing the Umbilical Cord at Birth in Preterm Infants
2020, Journal of Pediatrics
To evaluate the rates of practice, and the associations between different cord management strategies at birth (delayed cord clamping [DCC], umbilical cord milking [UCM], and early cord clamping [ECC]) and mortality or major morbidity, rates of blood transfusion, and peak serum bilirubin in a large national cohort of very preterm infants.
We retrospectively studied preterm infants <33 weeks of gestation admitted to the Canadian Neonatal Network between January 2015 and December 2017. Patients who received ECC (<30 seconds), UCM, or DCC (≥30 seconds) were compared. Multiple generalized linear/quantile logistic regression models were used.
Of 12 749 admitted infants, 9729 were included; 4916 (50.5%) received ECC, 394 (4.1%) UCM, and 4419 (45.4%) DCC. After adjustment for potential confounders identified between groups in univariate analyses, the odds of mortality or major morbidity were higher in the ECC group when compared with UCM group (aOR, 1.18; 95% CI, 1.03-1.35). Mortality and intraventricular hemorrhage were associated with ECC as compared with DCC (aOR, 1.6 [95% CI, 1.22-2.1] and aOR, 1.29 [95% CI, 1.19-1.41], respectively). The odds of severe intraventricular hemorrhage were higher with UCM compared with DCC (aOR, 1.38; 95% CI, 1.05-1.81). Rates of blood transfusion were higher with ECC compared with UCM and DCC (aOR, 1.67 [95% CI, 1.31-2.14] and aOR, 1.68 [95% CI, 1.35-2.09], respectively), although peak serum bilirubin levels were not significantly different.
Both DCC and UCM were associated with better short-term outcomes than ECC; however, the odds of severe intraventricular hemorrhage were higher with UCM compared with DCC.
Implementation of Delayed Cord Clamping in Vigorous Preterm Neonates
2018, JOGNN - Journal of Obstetric, Gynecologic, and Neonatal Nursing
Citation Excerpt :
Furthermore, the incidence of blood transfusions in preterm neonates was significantly lower as a result of the hemodynamic effects of DCC (Backes et al., 2014; Garofalo & Abenhaim, 2012; Rabe et al., 2012; WHO, 2014). An additional prominent positive outcome reported in the research was improved hematocrit levels during the first few days of life (Jelin et al., 2015; Krueger et al., 2015; Oh et al., 2011). Hence, DCC is essential to ensure hemodynamic stability in preterm neonates.
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.
Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis
2018, American Journal of Obstetrics and Gynecology
Citation Excerpt :
About 15 million children are born <37 weeks’ gestation annually, of whom about 1 million die.4 Several publications in this journal have addressed whether enhanced placental transfusion–by delayed clamping of the umbilical cord, milking the cord before or after clamping, or a combination of these measures–can reduce adverse neonatal outcomes, including death.5-10 Delaying umbilical cord clamping may improve outcome in preterm infants by increasing the volume of blood transferred from placenta to infant11 and by allowing time for physiologic transition.12
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.
No. 347-Obstetric Management at Borderline Viability
2017, Journal of Obstetrics and Gynaecology Canada
Citation Excerpt :
Delayed cord clamping has been adopted as an intervention to help minimize blood transfusion and improve outcomes in preterm births. Several studies and meta-analyses have shown improvement in short-term outcomes, significantly lower rates of blood transfusion, and trends towards decreased rates of IVH and sepsis in infants who underwent delayed cord clamping or cord milking.50,51 Studies reporting benefit with delayed cord clamping report protocols ranging from 20 to 180 seconds of delay.52,53
The primary objective of this guideline was to develop consensus statements to guide clinical practice and recommendations for obstetric management of a pregnancy at borderline viability, currently defined as prior to 25+6 weeks.
Clinicians involved in the obstetric management of women whose fetus is at the borderline of viability.
Women presenting for possible birth at borderline viability.
This document presents a summary of the literature and a general consensus on the management of pregnancies at borderline viability, including maternal transfer and consultation, administration of antenatal corticosteroids and magnesium sulfate, fetal heart rate monitoring, and considerations in mode of delivery. Medline, EMBASE, and Cochrane databases were searched using the following keywords: extreme prematurity, borderline viability, preterm, pregnancy, antenatal corticosteroids, mode of delivery. The results were then studied, and relevant articles were reviewed. The references of the reviewed studies were also searched, as were documents citing pertinent studies. The evidence was then presented at a consensus meeting, and statements were developed.
The content and recommendations were developed by the consensus group from the fields of Maternal-Fetal Medicine, Neonatology, Perinatal Nursing, Patient Advocacy, and Ethics. The quality of evidence was rated using criteria described in the Grading of Recommendations Assessment, Development and Evaluation methodology framework (reference 1). The Board of the Society of Obstetricians and Gynaecologists of Canada approved the final draft for publication.
The quality of evidence was rated using the criteria described in the Grading of Recommendations, Assessment, Development, and Evaluation methodology framework. The interpretation of strong and weak recommendations is described later. The Summary of Findings is available upon request.
A multidisciplinary approach should be used in counselling women and families at borderline viability. The impact of obstetric interventions in the improvement of neonatal outcomes is suggested in the literature, and if active resuscitation is intended, then active obstetric interventions should be considered.
Evidence will be reviewed 5 years after publication to decide whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations.
This guideline was developed with resources funded by the Society of Obstetricians and Gynaecologists of Canada and the Women and Babies Program at Sunnybrook Health Sciences Centre.
- 1.
  Women facing decisions regarding obstetric and neonatal management at extremely preterm gestations should be counselled by an expert multidisciplinary team. Neonatal survival data vary globally, and national and local data are important elements of counselling. The data should be interpreted with the understanding that perinatal management has a role to play in these results (Weak, Moderate).
- 2.
  Whenever possible, women at periviable gestations should be offered transfer to a level 3 centre. If a clear, informed decision has been reached not to provide the infant with intensive care if delivered, and if specialized comfort care can be provided at the referring centre, the transfer may not be necessary. Decision to transfer should factor in gestational age, estimated fetal weight, and parental preferences. Practitioners should be educated about the management options for extreme prematurity and should have the option to call specialist practitioners for advice in managing these cases. Care providers should acknowledge the difficulty and disruption associated with transfer and should prepare women and their families for the process and potential outcomes (Strong, Moderate).
- 3.
  First trimester ultrasound should be offered in all pregnancies, especially when risk factors for preterm birth are present. The value of ultrasound-measured estimated fetal weight in decision-making around obstetric interventions requires study (Strong, Low).
- 4.
  In the periviable periods, antenatal corticosteroids should be administered after careful consideration of the likelihood of delivery and the resuscitation wishes of the family. If delivery is expected within 7 days, and if full resuscitation is planned, a single course of antenatal corticosteroids should be administered to women (Strong, Moderate).
- 5.
  A rescue dose of corticosteroid, when the initial course of corticosteroid was given before 25 weeks, should not currently be recommended because benefit or harm of such additional dose is not proven. Further study is required (Strong, Moderate).
- 6.
  Magnesium sulfate for neuroprotection should be given after careful consideration of the likelihood of delivery and the benefits of treatment. If delivery is expected imminently, and if full resuscitation is planned, magnesium sulfate should be administered in the extreme preterm population in accordance with local protocols and the existing SOGC guideline (Strong, Moderate).
- 7.
  Other than for maternal indications, routine Caesarean delivery in the extreme preterm population should be avoided (Strong, High). In cases of fetal malpresentation or other obstetric indications, the limitations of evidence should be discussed and a multidisciplinary approach should be used to come to a decision that considers both maternal and fetal outcome when active neonatal management is planned (Strong, Moderate).
- 8.
  Intrapartum continuous fetal monitoring should be used when active neonatal management in planned. Interpretation parameters should be used cautiously by those experienced in the care of preterm and extremely preterm gestations (Weak, Low).
- 9.
  Delayed cord clamping in the extreme preterm population is recommended. When this is not feasible, cord milking should be considered (Strong, Moderate).
Focus on placental transfusion for preterm neonates: Delayed cord clamping and/or milking?
2016, Gynecologie Obstetrique et Fertilite
Malgré les grandes avancées en périnatologie, l’anémie du prématuré reste une complication fréquente. Les bénéfices d’un clampage retardé du cordon (d’au moins 30 secondes selon les recommandations) sont particulièrement bien établis chez le nouveau-né prématuré en, augmentant de façon significative le taux d’hématocrite et d’hémoglobine à la naissance et en réduisant le recours transfusionnel et les hémorragies intraventriculaires. Cette pratique est également associée à un meilleur équilibre hémodynamique initial. Le clampage retardé du cordon peut être difficile à mettre en œuvre en cas de mauvaise adaptation à la vie extra-utérine. Pour ne pas retarder les manœuvres de réanimation, la technique du « milking » ou « traite » du cordon a été proposée comme alternative au clampage retardé. Elle apparaît comme une procédure intéressante, facile et sûre pouvant être à la fois pratiquée par un obstétricien ou un pédiatre, avec des bénéfices comparables tant sur les plans hémodynamique, hématologique que neurologique. Néanmoins, les techniques de transfusions placentaires sont encore à clarifier de même que leurs bénéfices à long terme notamment sur le devenir neurodéveloppemental de ces enfants prématurés.
Anemia of prematurity remains a common complication despite recent advances in perinatal and neonatal medicine. The delayed cord clamping (at least 30 seconds as recommended) has several benefits: increased hemoglobin and hematocrit levels at birth, improved initial hemodynamic, decreased incidence of transfusions and intraventricular hemorrhages. When the birth transition is difficult, wait 30 seconds before clamping can be impossible. So as not to interfere with the neonatal resuscitation, the “milking” has been proposed as an alternative method to the delayed cord clamping. This is a safe and easy method, which can be done either by an obstetrician or pediatrician with comparable results for the child on his hemodynamic, hematological and neurological status. It still lacks technical information on this method and neurodevelopmental outcomes of these preterm infants.

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: The authors report no conflict of interest.

: Cite this article as: Krueger MS, Eyal FG, Peevy KJ, et al. Delayed cord clamping with and without cord stripping: a prospective randomized trial of preterm neonates. Am J Obstet Gynecol 2015;212:394.e1-5.

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Meeting paperCAOG paperDelayed cord clamping with and without cord stripping: a prospective randomized trial of preterm neonates

Objective

Study Design

Results

Conclusion

Section snippets

Materials and Methods

Results

Comment

Lancet

Placental Transfusion and hyperbilirubinemia in the premature

Pediatrics

The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized controlled trial

Pediatrics

Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomized controlled trial

BMJ

Effects of delayed cord clamping in very-low-birth-weight infants

J Perinatol

Placental transfusion umbilical cord clamping and preterm infants

J Perinatol

Meeting paper
CAOG paper
Delayed cord clamping with and without cord stripping: a prospective randomized trial of preterm neonates