Video Abstract

Video Abstract

Close modal
CONTEXT:

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

OBJECTIVE:

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

DATA SOURCES:

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.

STUDY SELECTION:

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

DATA EXTRACTION:

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

RESULTS:

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.

LIMITATIONS:

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

CONCLUSIONS:

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.

Immaturity of multiple organ systems puts preterm infants born at <34 weeks’ gestation at high risk for mortality and morbidities, such as intraventricular hemorrhage (IVH), and they are more likely to need resuscitation and stabilization at birth compared with those born late preterm or at term.1  They therefore require different policies and management than infants born late preterm or term.

Umbilical cord management affects every one of the 15 million infants born preterm annually.2,3  There is growing evidence that umbilical cord management at birth may influence survival, and major neonatal morbidities associated with preterm birth.48  Currently, there are several alternative cord management strategies, including deferring clamping on the basis of timing or consideration of the infants’ respiratory status (from here on referred to as delayed cord clamping [DCC]) or milking the intact or cut cord.9 

Several mechanisms are proposed to explain how cord management might influence infant mortality and morbidity. At the time of birth ∼30% of the fetal-placental circulation is outside the fetus.10  If the cord is not clamped immediately at birth, blood flow between the placenta and the infant may continue, which may increase placental transfusion, the net transfer of blood from the placenta to the infant. Cord management at birth impacts not only the volume of placental transfusion to the infant but also the cardiovascular transition around the onset of breathing and/or ventilation.1113  Early cord clamping (ECC) before establishment of respiration may be associated with major hemodynamic consequences especially in extremely preterm and nonvigorous infants who are at high risk of brain injuries.12,1416 

In a statement in 2015, the International Liaison Committee on Resuscitation (ILCOR) gave a weak recommendation for delayed umbilical cord clamping for preterm infants not requiring immediate resuscitation after birth.17  In the statement, they identified many knowledge gaps regarding cord management for both infant and maternal outcomes. To derive stronger recommendations, more evidence is required on existing strategies (such as DCC and milking of the intact or cut cord) and innovative techniques (such as resuscitation with intact cord) in a variety of neonatal populations. There have been many randomized controlled trials (RCTs) published since the latest ILCOR recommendations in 2015, including the largest to date addressing DCC at preterm birth.18 

This systematic review and meta-analysis includes this latest evidence. Simultaneously, the ILCOR Consensus on Science with Treatment Recommendations was completed in collaboration with the Cochrane Neonatal group. This will be published separately.

To determine the effects of different umbilical cord management strategies (including timing of clamping and cord milking) at preterm birth <34 weeks’ gestational age.

This review was conducted by following the methodology outlined in the Cochrane Handbook for Systematic Reviews of Interventions and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines.19,20  The protocol was registered prospectively with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42019155475). Full methods are detailed in Appendix 1 in Supplemental Information.

We considered all RCTs and cluster RCTs in which researchers compared alternative umbilical cord management strategies at preterm birth <34 weeks’ gestational age or with low birth weight <2500 g. Studies were included if the authors reported a mean gestational age of <34 weeks or if >80% of the births were <34 weeks’ gestation.

Studies in which researchers compare the following umbilical cord management interventions were included in this review:

  1. ECC, defined as application of a clamp to the cord <30 seconds after birth, without cord milking;

  2. DCC, defined as application of a clamp to the cord ≥30 seconds after birth or based on physiologic parameters (such as when cord pulsation has ceased or breathing has been initiated), without cord milking;

  3. intact-cord milking (ICM) (also referred to as “stripping”), defined as repeated compression of the cord from the placental side toward the infant with the connection to the placenta intact at any time point within the first few minutes after birth; and

  4. cut-cord milking (CCM) (also referred to as “stripping”), defined as drainage of the cord by compression from the cut end toward the infant after clamping and cutting a long segment.

Review outcomes were selected in consultation with representatives from the World Health Organization and ILCOR. They comprised infant and maternal outcomes that were seen as clinically relevant and therefore likely to change clinical practice.21  All outcomes and their definitions have been summarized in Table 1. Prespecified subgroup analyses, search strategy, study selection, data extraction, risk of bias evaluation, certainty of evidence assessment, and data synthesis are detailed in Appendix 1 in Supplemental Information.

Forty-two studies (reported in 102 articles) including 5772 infants met the inclusion criteria for the review, of which 41 studies (including 5676 infants) had data that could be included in the meta-analysis (Fig 1, Appendix 3 in Supplemental Information: full list of included studies per comparison).

Study characteristics and participant characteristics for the included studies are outlined for each comparison in Tables 1a–1d in the Supplemental Information and Tables 25, respectively.

All of the included studies were individual RCTs (unit of randomization was either the mother or the infant). Studies were undertaken in a range of countries (although most were high income by World Bank country classifications22). Most studies excluded infants with complications such as major malformations or congenital anomalies.

Risk of bias is summarized in Fig 2. The majority of studies were at low risk of selection bias (62% low for random sequence generation, 71% low for allocation concealment). All included studies were at high risk of performance bias, because it is difficult, if not impossible, to blind the clinicians managing the infant’s care. Blinding of outcome assessment was rated separately for delivery room outcomes and outcomes assessed at a later stage. Although risk of bias was high across all studies for delivery room outcomes (because of the nature of the intervention), it was low for most studies (55%) for other outcomes. Most studies were at low risk of attrition bias. There were some concerns regarding selective outcome reporting bias. Evidence profile tables were collated for primary and key secondary outcomes applying the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. These include details on risk of bias (Tables 2–5 in Supplemental Information).

Comparison 1: DCC Compared to ECC

We identified 23 studies including 3514 infants comparing DCC to ECC. Studies were undertaken in a range of countries, mostly high-income. Most studies included births before 32 to 34 weeks’ gestation and were conducted at a single center (78%), but the largest RCTs were multicenter (22%). The studies covered a variety of timings of cord clamping and positioning of the infant. Timing of DCC ranged between 30 and ≥120 seconds, with half the studies (52%) delayed by 30 to 45 seconds. Timing of early or immediate cord clamping ranged from within 5 seconds to within 30 seconds across studies; in most studies (69%), clamping was within 10 seconds.

Results for all primary and key outcomes are summarized in Table 6. Compared to ECC, DCC may improve neonatal survival (or reduce neonatal mortality) or may make no difference (survival: risk ratio [RR]: 1.02, 95% confidence interval [CI]: 1.00 to 1.04 (Fig 3); Number needed to benefit: 50, 95% CI: 25 to no benefit; 16 studies, 2988 infants; I2 = 0%, certainty of evidence moderate). This translates into an RR of 0.80 (95% CI: 0.63 to 1.02) for the inverse outcome of mortality (post hoc analysis, Table 6 in Supplemental Information).

There was no clear difference in the number of infants with severe IVH (RR: 0.98, 95% CI: 0.67 to 1.42) and necrotizing enterocolitis (NEC) (RR: 0.83, 95% CI: 0.61 to 1.13). There was little to no difference for chronic lung disease (RR: 1.03, 95% CI: 0.94 to 1.13) and hyperbilirubinemia treated by phototherapy (RR: 0.99, 95% CI: 0.95 to 1.03).

DCC probably improves hematologic measures. Peak hemoglobin and hematocrit (%) were probably higher for DCC compared to ECC within 24 hours after birth (peak hemoglobin: mean difference [MD]: 1.24 g/dL, 95% CI: 0.01 to 2.47; peak hematocrit: MD: 2.63%, 95% CI: 1.85 to 3.42), and peak hematocrit was higher within 7 days after birth (MD: 2.70%, 95% CI: 1.88 to 3.52).

The evidence was unclear for survival without moderate or severe neurodevelopmental impairment in early childhood (RR: 0.96, 95% CI: 0.78 to 1.17). None of the included studies assessed other early childhood outcomes. Compared to ECC, DCC may make little or no difference to maternal complications, including any postpartum hemorrhage ≥500 mL (RR: 0.93, 95% CI: 0.54 to 1.62), severe postpartum hemorrhage ≥1000 mL, use of therapeutic uterotonic agents, blood transfusion, manual removal of the placenta, or postpartum infection (Table 6). No researchers reported on maternal deaths, severe morbidity, or additional treatment of postpartum hemorrhage. Authors of 1 study reported on mothers’ views and experiences.23,24 

Other outcomes are detailed in Table 7a in Supplemental Information. Few differences were found except for hematologic outcomes. Compared with infants in the ECC group, infants in the DCC group had less inotropic support for hypotension during the first 24 hours of life (RR: 0.36, 95% CI: 0.17 to 0.75), a higher measurement of lowest mean arterial blood pressure in the first 12 hours of life (MD: 1.79 mm Hg, 95% CI: 0.53 to 3.05), lower incidence of any blood transfusion (RR: 0.83, 95% CI: 0.77 to 0.90), and a lower total number of blood transfusions per infant (MD: −0.63, 95% CI: −1.08 to −0.17) during hospital course.

Comparison 2: ICM Compared to ECC

We identified 13 studies comparing ICM to ECC (Table 3). Studies in comparison 2 included 1170 infants, and all were single center. Two studies (18%) included only preterm births <30 weeks. Timing of ECC ranged between clamping immediately and within 20 seconds of birth, and in most studies (69%), clamping was immediately. For ICM, the cord was milked between 2 and 4 times, with most studies (54%) reporting milking 3 times.

Compared to ECC, ICM may make no difference, slightly decrease, or slightly improve survival to discharge (RR: 1.02, 95% CI: 0.98 to 1.06; I2 = 24%, 10 studies, 945 infants; certainty of evidence moderate) (Fig 4). This translates into an RR of 0.77 (95% CI: 0.49 to 1.23) for the inverse outcome of mortality (post hoc analysis, Table 6 in Supplemental Information).

We found no clear difference for severe IVH (RR: 0.72, 95% CI: 0.44 to 1.19), chronic lung disease (RR: 1.02, 95% CI: 0.63 to 1.65), and NEC (RR: 0.80, 95% CI: 0.55 to 1.18), and there was little or no difference for hyperbilirubinemia treated by phototherapy (RR: 1.04, 95% CI: 0.94 to 1.16).

ICM probably improves hematologic measures within 24 hours after birth. Peak hemoglobin and hematocrit (%) were higher for ICM compared to ECC within 24 hours after birth (peak hemoglobin: MD: 1.18 g/dL, 95% CI: 0.65 to 1.71; peak hematocrit: MD: 3.04%, 95% CI: 1.28 to 4.80). Evidence was uncertain for peak hematocrit and hemoglobin within 7 days after birth.

Limited data are available regarding outcomes in later infancy. Certainty of evidence was very low for moderate to severe neurodevelopmental impairment in early childhood (RR: 0.75, 95% CI: 0.21 to 2.71) and cerebral palsy in early childhood (RR: 2.65, 95% CI: 0.88 to 7.97). There were no researchers assessing sensory outcomes in later infancy.

The evidence is uncertain about maternal complications, including severe postpartum hemorrhage ≥1000 mL or blood transfusion, and there were no researchers assessing other maternal complications such as postpartum hemorrhage ≥500 mL (Table 7).

Other outcomes are detailed in Table 7b in Supplemental Information. In infants, few differences were found, with the exception of less inotropic support for hypotension during the first 24 hours of life (RR: 0.61, 0.44 to 0.84) and fewer infants receiving ≥1 blood transfusion (RR: 0.73, 95% CI: 0.56 to 0.94) in the ICM group.

Comparison 3: CCM Compared to ECC

We identified 1 single-center study of 60 infants evaluating CCM compared to ECC. The evidence was uncertain for the incidence of survival or its inverse mortality to hospital discharge, with no deaths in either group (Table 8). Evidence was also uncertain for severe IVH (RR: 0.33, 95% CI: 0.01 to 7.87), chronic lung disease (RR: 1.00, 95% CI: 0.07 to 15.26), and NEC (RR: 0.50, 95% CI: 0.05 to 5.22). CCM may increase peak hematocrit concentrations within 24 hours after birth (MD: 3.34%, 95% CI: 0.60 to 6.08). The authors of the study did not report other hematologic measures and did not assess any of the included early childhood or maternal outcomes. Other outcomes are detailed in Table 7c in Supplemental Information.

Comparison 4: DCC Compared to ICM

We identified 7 studies including 1073 infants comparing DCC to ICM. The studies were published between 2011 and 2019, and most were single center (71%). Timing of DCC ranged between 30 and 180 seconds, and most studies (71%) reported delay of 30 to 60 seconds. For ICM, the cord was milked between 3 and 4 times, with most studies (71%) reporting milking 4 times.

Compared to ICM, DCC may make no difference, slightly decrease, or slightly improve survival to discharge (RR: 0.99, 95% CI: 0.95 to 1.02; I2 = 14%; 5 studies, 1000 infants, certainty of evidence moderate) (Fig 5, Table 9). This translates into an RR of 1.21 (95% CI: 0.76 to 1.94) for the inverse outcome of mortality (post hoc analysis, Table 6 in Supplemental Information).

There were no clear differences for key neonatal morbidities of severe IVH (RR: 0.60, 95% CI: 0.32 to 1.12), chronic lung disease (RR: 0.91, 95% CI: 0.67 to 1.25), NEC (RR: 1.57, 95% CI: 0.83 to 2.97), and hyperbilirubinemia treated phototherapy (RR: 1.05, 95% CI: 0.90 to 1.24).

There were also no clear differences between DCC and ICM for hematologic measures within 24 hours (peak hemoglobin concentrations [g/dL]: MD: −0.02, 95% CI: −0.56 to 0.53, peak hematocrit concentrations [%] MD: −0.18, 95% CI: −1.90 to 1.54). No study authors reported data on peak hemoglobin or peak hematocrit concentration within 7 days after birth.

Limited data were available regarding outcomes in later infancy. Certainty of evidence was low for moderate to severe neurodevelopmental impairment (RR: 0.22, 95% CI: 0.01 to 4.40), cerebral palsy in early childhood (RR: 0.36, 95% CI: 0.01 to 8.65), and significant developmental delay in early childhood (RR: 14.06, 95% CI: 0.83 to 237.84). Researchers of 1 study assessed legal blindness and reported no events, and no researchers assessed hearing deficits.

No researchers reported the included maternal outcomes. Other outcomes are detailed in Table 7d in Supplemental Information. Few differences were found between ICM and DCC.

Comparisons 5 to 8

No studies were identified for any of these comparisons (DCC versus CCM, ICM versus CCM, DCC <60 seconds versus DCC ≥60 seconds, time-based DCC versus physiologic DCC).

No patterns were identified in the subgroup analyses (Table 8 in Supplemental Information). The number of prespecified subgroup analyses was large, and P values were not adjusted for multiple comparisons. Researchers of only 2 studies reported data by subgroup, limiting the ability to perform subgroup analyses.

In this systematic review and meta-analysis, we identified 42 eligible studies with 5722 infants comparing cord management interventions. Compared to early clamping, delayed clamping may slightly improve infant survival but may make no difference (moderate quality evidence). We found moderate- to high-quality evidence that delayed clamping does not reduce or increase major neonatal morbidities, but it probably improves hematologic measures and may reduce the use of inotropes and blood transfusions in infants.

Compared to early clamping, intact milking may result in increased survival, slightly reduced survival, or make no difference. We found low to moderate quality evidence indicating no clear difference in major neonatal morbidities such as chronic lung disease, IVH, and NEC. Intact milking probably improves hematologic measures.

For the 1 study in which researchers compared ECC to CCM, the evidence was uncertain for infant survival and major morbidities. CCM may increase peak hematocrit within 24 hours after birth.

Compared to ICM, delayed clamping probably results in little to no difference in survival, major neonatal morbidities, and hematologic measures.

Across all comparisons, many of the infants could not be classified into the correct subgroup categories, and thus, meaningful subgroup differences are not possible to detect with the current data.

The latest comprehensive review in this area was a Cochrane review with searches conducted in November 2017.8  Authors of that review found a reduction in infant death for delayed compared to early clamping, a slight reduction in any IVH, but no reduction in severe IVH. There was insufficient evidence to derive conclusions for cord milking. With our review, we add new information, because we identified and included 11 additional recently published trials.2535 

Although previous reviews included preterm infants born at less than 37 weeks’ gestational age,4,8  our review is limited to infants born at less than 34 weeks’. Although late preterm infants have increased risk for admission to neonatal intensive care and poor developmental outcome compared with term infants, they do not have the same serious morbidities experienced by less mature preterm infants.36  Therefore, 18 studies included in the Cochrane review were excluded from the current review, leading to a slightly smaller total number of infants (188 less), despite the 11 additional trials.

Previous reviews included infant mortality as a primary outcome, whereas in this review, we assess the inverse of mortality, survival, because this is the standard ILCOR approach. This changes the relative effect measures, as shown in our post hoc sensitivity analysis comparing RRs for survival and mortality using the same data (Table 6 in Supplemental Information). The reason for this is that relative risk depends on the incidence of an event, which is higher for survival than mortality. Thus, the same absolute number of deaths can translate into different relative risk estimates for survival or mortality. For instance, in comparison 1, in the delayed clamping group, 1383 (93%) infants survived and 107 (7%) died. In the early clamping group, 1364 (91%) infants survived and 134 (9%) died. This equals a 2% absolute difference for both survival (93% to 91% = 2%) and mortality (9% to 7% = 2%). However, because survival was more common than mortality, the relative risk indicates a small 2% increase in survival (RR: 0.93/0.91 = 1.02) but a much larger 20% relative risk reduction for mortality (RR: 0.07/0.09 = 0.80).

For comparison 1 (early versus delayed clamping), the relative risk for mortality (indicating a 20% reduction) is similar to that reported in previous reviews (eg, 27% relative risk reduction in the Cochrane review).8  Although for previous reviews, this finding was statistically significant, in the current review, the CI touches the line of no effect. This may be due to different eligibility criteria for gestational age (as outlined above) or to the more-recent studies included in the current review. We did not find a difference in survival between ICM and delayed clamping (comparison 4). Point estimates for survival with intact milking compared to early clamping (comparison 2) are similar to point estimates for delayed compared to early clamping (comparison 1), but CIs are wider in comparison 2 because of fewer included studies. This suggests that intact milking may be comparable to delayed clamping for the outcome of survival, but more evidence is needed to confirm this.

In this review, we find improved hematologic measures and reduced use of inotropes for delayed clamping, and intact and cut milking compared to early clamping, in accordance with previous reviews.4,8,13  This supports the proposed mechanism of placental transfusion (ie, increased net transfer of blood from the placenta to the infant) through delayed clamping or milking.10,37  Our findings did not suggest a difference between delayed clamping and milking with respect to hematologic measures.

Although authors of previous reviews report differences in IVH rates for different cord management strategies,8  we did not find evidence for this in the current review. Animal models have been used to demonstrate that during umbilical cord milking, there was an increase in carotid blood flow and pressure.26  In addition, a recent trial comparing delayed clamping to milking was stopped early in the subgroup of very preterm infants (<28 weeks’ gestation), because of a higher incidence of severe IVH in the milking group.26  Thus, there may be different IVH risks related to cord management strategies depending on gestational age. Further evidence is required to resolve this question. In addition, not all studies in the current review were blinded for assessment of IVH, which is problematic because ultrasound diagnosis of IVH can be rater-dependent.38  Consequently, we downgraded certainty of evidence for this outcome.

Few researchers reported developmental outcomes in early childhood, and the evidence was uncertain for all comparisons. One study published outcomes in early childhood for early clamping compared to delayed clamping (comparison 1) shortly after our search date and was therefore not included in the analysis.39  Authors of this study found that delayed clamping may reduce the risk of death or adverse neurodevelopmental outcome at 2 years of age for children born <32 weeks, but confirmation in larger studies is needed.

Cord management at preterm birth is an active research field, evidenced by the number of additional studies included in this review compared to previous reviews. The searches for the latest Cochrane update were conducted in November 2017.8  In <2 years (search to July 2019), we identified 11 new studies. Still, more evidence is being generated; a search in February 2019 identified an additional 62 ongoing trials evaluating cord management strategies in preterm infants.40 

Ultimately, we want to answer the question: “which cord management strategy is the best and for whom?” With the current study, we take a step toward answering this question by looking at different comparisons analyzed in pairwise meta-analyses. Yet, there is insufficient evidence, when using aggregate data, to derive a definite answer, particularly when assessing differences for key infant subgroups. Once ongoing trials are completed, a network meta-analysis will be possible, which allows comparing and ranking of multiple interventions simultaneously.41  For assessing differential treatment effects across subgroups, the use of individual participant data can increase statistical power and reduce the risk of ecological bias.42  The individual participant data on Cord Management at Preterm Birth (iCOMP) Collaboration is collating individual participant data from ongoing and completed trials to perform network meta-analysis and subgroup analyses to resolve remaining questions.40  Investigators planning future trials in this area should follow a prospective meta-analysis framework in collaboration with the iCOMP Collaboration to target evidence gaps and avoid research waste.43 

Strengths of this review include its rigorous methods, including a prospectively registered protocol, a comprehensive search strategy, two reviewers independently completing each step of the review process, and the use of GRADE to determine certainty of evidence.44  The author team constitutes a collaboration of world experts in systematic reviews, neonatology, and obstetrics, including the ILCOR taskforce, the Cochrane Neonatal and Pregnancy and Childbirth groups, and independent experts in cord management.

Yet, there are several limitations. For many reported comparisons and outcomes, certainty of evidence was low or very low, or no studies were available. This was mainly due to imprecision and, in some cases, due to inconsistency and risk of bias. For four of the prespecified comparisons, no studies were identified. In this review, only pairwise comparisons are presented; we did not conduct analyses comparing all available comparisons simultaneously (network meta-analysis). Our subgroup analyses were limited by authors of most studies not reporting outcomes separately by subgroup, highlighting the need for individual participant data to resolve these questions. Definitions for early and delayed clamping and milking varied across studies. Delayed clamping ranged from 30 seconds to >2 minutes, and early clamping ranged from within 5 seconds to within 30 seconds. Thus, in some instances, early and delayed clamping groups may have received similar interventions.

DCC at preterm birth may be beneficial compared to early clamping, and these benefits appear to be hemodynamic, but additional evidence is required to confirm this. There is some evidence that ICM may be similarly beneficial, but this needs further study. Additional evidence from ongoing trials and individual participant data network meta-analysis is required to determine which cord management strategies are the most advantageous and for whom.

We thank Carol Friesen (Cochrane Neonatal) for developing and conducting literature searches. We thank the following members of the ILCOR Scientific Advisory Committee and Neonatal Life Support Task Force for their input and assistance in developing the protocol and offering feedback on the review: Myra H. Wyckoff, MD, chair; Jonathan Wyllie MBChB, BSC, vice chair; Maria Fernanda de Almeida, MD; Jorge W. Fabres, MD; Joe Fawke, MD; Ruth Guinsburg, MD, PhD; Shigeharu Hosono, MD, PhD; Tetsuya Isayama, MD, MSc, PhD; Vishal S. Kapadia, MD, MSCS; Han-Suk Kim, MD, PhD; Helen G. Liley, MBChB; Chris JD McKinlay, MBChB, PhD; Lindsay Mildenhall, MBChB; Jeffrey M. Perlman, MBChB; Yacov Rabi, MD; Charles C. Roehr, MD, PhD; Edgardo Szyld, MD, MSc; Daniele Trevisanuto, MD; Sithembiso Velaphi, MBChB, FC Ped, PhD; and Gary Weiner, MD. We also thank Slavica Berber, PhD, Sol Libesman, BSc, Kylie Hunter, MSc, Angie Barba, MSc, Mason Aberoumand, MSc, and Hannah Ahern, MSc (National Health and Medical Research Council Clinical Trials Centre, University of Sydney) for assistance in the review process.

Ms Seidler conceptualized the protocol, designed the data collection forms, selected studies for inclusion, extracted data, assessed risk of bias and certainty of evidence, conducted the analyses, drafted the initial manuscript, and reviewed and revised the manuscript; Ms Gyte conceptualized the protocol, designed the data collection forms, selected studies for inclusion, extracted data, assessed risk of bias and certainty of evidence, conducted the analyses and reviewed the manuscript; Ms Ovelman assisted with protocol development and study selection, checked data extractions, risk of bias assessments, conducted subgroup analyses and reviewed and prepared the manuscript; Dr Soll conceptualized the protocol, supervised study selection, data extraction, risk of bias and certainty of evidence assessments, and data analyses, and drafted, reviewed and revised the manuscript; Drs Rabe, Díaz-Rossello, Duley, Aziz, Testoni Costa-Nobre, Davis, Schmölzer, and Askie conceptualized the protocol and critically reviewed the manuscript for important intellectual content; and all authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

This protocol has been registered with the International Prospective Register of Systematic Reviews (https://www.crd.york.ac.uk/prospero/) (identifier CRD42019155475).

FUNDING: Funded by the American Heart Association, on behalf of the International Liaison Committee on Resuscitation for article submission to the editor. This review has also been supported in part by the Vermont Oxford Network. Funded by the National Institutes of Health (NIH).

CCM

cut-cord milking

CI

confidence interval

DCC

delayed cord clamping

ECC

early cord clamping

GRADE

Grading of Recommendations Assessment, Development and Evaluation

ICM

intact-cord milking

ILCOR

International Liaison Committee on Resuscitation

IVH

intraventricular hemorrhage

MD

mean difference

NEC

necrotizing enterocolitis

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

RCT

randomized controlled trial

RR

risk ratio

1
Weiner
GM
,
Zaichkin
J
;
American Academy of Pediatrics
;
American Heart Association
.
Textbook of Neonatal Resuscitation (NRP)
, 7th ed.
Elk Grove Village, IL
:
American Academy of Pediatrics
;
2016
2
Blencowe
H
,
Cousens
S
,
Oestergaard
MZ
, et al
.
National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications
.
Lancet
.
2012
;
379
(
9832
):
2162
2172
3
World Health Organization
;
March of Dimes
;
The Partnership for Maternal, Newborn & Child Health
;
Save the Children
.
Born Too Soon: The Global Action Report on Preterm Birth
.
Geneva, Switzerland
:
World Health Organization
;
2012
4
Fogarty
M
,
Osborn
DA
,
Askie
L
, et al
.
Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis
.
Am J Obstet Gynecol
.
2018
;
218
(
1
):
1
18
5
Rabe
H
,
Sawyer
A
,
Amess
P
,
Ayers
S
;
Brighton Perinatal Study Group
.
Neurodevelopmental outcomes at 2 and 3.5 years for very preterm babies enrolled in a randomized trial of milking the umbilical cord versus delayed cord clamping
.
Neonatology
.
2016
;
109
(
2
):
113
119
6
Al-Wassia
H
,
Shah
PS
.
Efficacy and safety of umbilical cord milking at birth: a systematic review and meta-analysis
.
JAMA Pediatr
.
2015
;
169
(
1
):
18
25
7
Mercer
JS
,
Erickson-Owens
DA
,
Vohr
BR
, et al
.
Effects of placental transfusion on neonatal and 18 month outcomes in preterm infants: a randomized controlled trial
.
J Pediatr
.
2016
;
168
:
50
55.e1
8
Rabe
H
,
Gyte
GML
,
Díaz‐Rossello
JL
,
Duley
L
.
Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes
.
Cochrane Database Syst Rev
.
2019
;(
9
):
CD003248
9
Katheria
A
,
Hosono
S
,
El-Naggar
W
.
A new wrinkle: umbilical cord management (how, when, who)
.
Semin Fetal Neonatal Med
.
2018
;
23
(
5
):
321
326
10
Farrar
D
,
Airey
R
,
Law
GR
,
Tuffnell
D
,
Cattle
B
,
Duley
L
.
Measuring placental transfusion for term births: weighing babies with cord intact
.
BJOG
.
2011
;
118
(
1
):
70
75
11
Rabe
H
,
Jewison
A
,
Alvarez
RF
, et al.;
Brighton Perinatal Study Group
.
Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial
.
Obstet Gynecol
.
2011
;
117
(
2 pt 1
):
205
211
12
Bhatt
S
,
Alison
BJ
,
Wallace
EM
, et al
.
Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs
.
J Physiol
.
2013
;
591
(
8
):
2113
2126
13
Yao
AC
,
Moinian
M
,
Lind
J
.
Distribution of blood between infant and placenta after birth
.
Lancet
.
1969
;
2
(
7626
):
871
873
14
Hooper
SB
,
Te Pas
AB
,
Lang
J
, et al
.
Cardiovascular transition at birth: a physiological sequence
.
Pediatr Res
.
2015
;
77
(
5
):
608
614
15
Kluckow
M
,
Hooper
SB
.
Using physiology to guide time to cord clamping
.
Semin Fetal Neonatal Med
.
2015
;
20
(
4
):
225
231
16
Niermeyer
S
,
Velaphi
S
.
Promoting physiologic transition at birth: re-examining resuscitation and the timing of cord clamping
.
Semin Fetal Neonatal Med
.
2013
;
18
(
6
):
385
392
17
Perlman
JM
,
Wyllie
J
,
Kattwinkel
J
, et al.;
Neonatal Resuscitation Chapter Collaborators
.
Part 7: neonatal resuscitation: 2015 international consensus on cardiopulmonary resuscitation and emergency cardiovascular care science with treatment recommendations
.
Circulation
.
2015
;
132
(
16
suppl 1
):
S204
S241
18
Tarnow-Mordi
W
,
Morris
J
,
Kirby
A
, et al.;
Australian Placental Transfusion Study Collaborative Group
.
Delayed versus immediate cord clamping in preterm infants
.
N Engl J Med
.
2017
;
377
(
25
):
2445
2455
19
Higgins
JPT
,
Altman
DG
,
Sterne
JAC
;
on Behalf of the Cochrane Statistical Methods Group and the Cochrane Bias Methods Group
. Assessing Risk of Bias in Included Studies. In:
Higgins
JPT
,
Churchill
R
,
Chandler
J
, eds.
Cochrane Handbook for Systematic Reviews of Interventions Version 5.2.0
.
2017
20
Moher
D
,
Liberati
A
,
Tetzlaff
J
,
Altman
DG
;
PRISMA Group
.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
.
J Clin Epidemiol
.
2009
;
62
(
10
):
1006
1012
21
Strand
ML
,
Simon
WM
,
Wyllie
J
,
Wyckoff
MH
,
Weiner
G
.
Consensus outcome rating for international neonatal resuscitation guidelines
.
Arch Dis Child Fetal Neonatal Ed
.
2020
;
105
(
3
):
328
330
22
The World Bank
.
World Bank country and lending groups.
2019
. Available at: http://data.worldbank.org/about/country-classifications/countryand-lending-groups. Accessed January 12, 2020
23
Bradshaw
L
,
Sawyer
A
,
Armstrong-Buisseret
L
,
Mitchell
E
,
Ayers
S
,
Duley
L
.
Cord pilot trial, comparing alternative policies for timing of cord clamping before 32 weeks gestation: follow-up for women up to one year
.
BMC Pregnancy Childbirth
.
2019
;
19
(
1
):
78
24
Bradshaw
L
,
Sawyer
A
,
Mitchell
E
,
Armstrong-Buisseret
L
,
Ayers
S
,
Duley
L
.
Women’s experiences of participating in a randomised trial comparing alternative policies for timing of cord clamping at very preterm birth: a questionnaire study
.
Trials
.
2019
;
20
(
1
):
225
25
Finn
D
,
Ryan
DH
,
Pavel
A
, et al
.
Clamping the Umbilical Cord in Premature Deliveries (CUPiD): neuromonitoring in the immediate newborn period in a randomized, controlled trial of preterm infants born at <32 weeks of gestation
.
J Pediatr
.
2019
;
208
:
121
126.e2
26
Katheria
A
,
Reister
F
,
Essers
J
, et al
.
Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants
.
JAMA
.
2019
;
322
(
19
):
1877
1886
27
Kazemi
MV
,
Akbarianrad
Z
,
Zahedpasha
Y
,
Haghshenas Mojaveri
M
,
Mehraein
R
.
Effects of delayed cord clamping on intraventricular hemorrhage in preterm infants
.
Iran J Pediatr
.
2017
;
27
(
5
):
e6570
28
Leal
VL
,
Bueno
LP
,
Vilaplana
LC
, et al
.
Effect of milking maneuver in preterm infants: a randomized controlled trial
.
Fetal Diagn Ther
.
2019
;
45
(
1
):
57
61
29
Li
J
,
Yu
B
,
Wang
W
,
Luo
D
,
Dai
QL
,
Gan
XQ
.
Does intact umbilical cord milking increase infection rates in preterm infants with premature prolonged rupture of membranes?
J Matern Fetal Neonatal Med
.
2020
;
33
(
2
):
184
190
30
Pratesi
S
,
Montano
S
,
Ghirardello
S
, et al
.
Placental circulation intact trial (PCI-T)-Resuscitation with the placental circulation intact vs. cord milking for very preterm infants: a feasibility study
.
Front Pediatr
.
2018
;
6
:
364
31
Ruangkit
C
,
Bumrungphuet
S
,
Panburana
P
,
Khositseth
A
,
Nuntnarumit
P
.
A randomized controlled trial of immediate versus delayed umbilical cord clamping in multiple-birth infants born preterm
.
Neonatology
.
2019
;
115
(
2
):
156
163
32
Shirk
SK
,
Manolis
SA
,
Lambers
DS
,
Smith
KL
.
Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial
.
Am J Obstet Gynecol
.
2019
;
220
(
5
):
482.e1
-
482.e8
33
Silahli
M
,
Duman
E
,
Gokmen
Z
,
Toprak
E
,
Gokdemir
M
,
Ecevit
A
.
The relationship between placental transfusion, and thymic size and neonatal morbidities in premature infants - a randomized control trial
.
J Pak Med Assoc
.
2018
;
68
(
11
):
1560
1565
34
Song
SY
,
Kim
Y
,
Kang
BH
,
Yoo
HJ
,
Lee
M
.
Safety of umbilical cord milking in very preterm neonates: a randomized controlled study
.
Obstet Gynecol Sci
.
2017
;
60
(
6
):
527
534
35
Engle
WA
,
Tomashek
KM
,
Wallman
C
;
Committee on Fetus and Newborn, American Academy of Pediatrics
.
“Late-preterm” infants: a population at risk
.
Pediatrics
.
2007
;
120
(
6
):
1390
1401
36
Boere
I
,
Roest
AA
,
Wallace
E
, et al
.
Umbilical blood flow patterns directly after birth before delayed cord clamping
.
Arch Dis Child Fetal Neonatal Ed
.
2015
;
100
(
2
):
F121
F125
37
Blank
DA
,
Polglase
GR
,
Kluckow
M
, et al
.
Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition
.
Arch Dis Child Fetal Neonatal Ed
.
2018
;
103
(
6
):
F539
F546
38
Hintz
SR
,
Slovis
T
,
Bulas
D
, et al
.
Interobserver reliability and accuracy of cranial ultrasound scanning interpretation in premature infants
.
J Pediatr
.
2007
;
150
(
6
):
592
596.e5
39
Armstrong-Buisseret
L
,
Powers
K
,
Dorling
J
, et al
.
Randomised trial of cord clamping at very preterm birth: outcomes at 2 years
.
Arch Dis Child Fetal Neonatal Ed
.
2020
;
105
(
3
):
292
298
40
Seidler
AL
,
Duley
L
,
Katheria
A
, et al
.
Systematic review and network meta-analysis with individual participant data on Cord Management at Preterm Birth (iCOMP): study protocol
.
BMJ Open
.
2020
;
10
(
3
):
e034595
41
Sutton
A
,
Ades
AE
,
Cooper
N
,
Abrams
K
.
Use of indirect and mixed treatment comparisons for technology assessment
.
Pharmacoeconomics
.
2008
;
26
(
9
):
753
767
42
Stewart
L
,
Tierney
J
,
Clarke
M
. Reviews of Individual Patient Data. In:
Higgins
JPT
,
Green
S
, eds.
Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0
.
London, United Kingdom
:
The Cochrane Collection
;
2011
43
Seidler
AL
,
Hunter
KE
,
Cheyne
S
,
Ghersi
D
,
Berlin
JA
,
Askie
L
.
A guide to prospective meta-analysis
.
BMJ
.
2019
;
367
:
l5342
44
Schünemann
HBJ
,
Brożek
J
,
Guyatt
G
,
Oxman
A
, eds..
GRADE Handbook. Handbook for Grading the Quality of Evidence and the Strength of Recommendations Using the GRADE Approach
.
The GRADE Working Group
;
2013
. Available at: https://gdt.gradepro.org/app/handbook/handbook.html#h.svwngs6pm0f2
45
Papile
LA
,
Burstein
J
,
Burstein
R
,
Koffler
H
.
Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights <1500 gm
.
J Pediatr
.
1978
;
92
(
4
):
529
534
46
Jobe
AH
,
Bancalari
E
.
Bronchopulmonary dysplasia
.
Am J Respir Crit Care Med
.
2001
;
163
(
7
):
1723
1729
47
Bell
MJ
,
Ternberg
JL
,
Feigin
RD
,
Keating
JP
,
Marshall
R
,
Barton
L
.
Neonatal necrotizing enterocolitis. Therapeutic decisions based upon clinical staging
.
Ann Surg
.
1978
;
187
(
1
):
1
7
48
Bayley
N.
Bayley Scales of Infant Development (BSID-II)
.
San Antonio, TX
:
Psychological Corporation
;
1993
49
de Vries
LS
,
Eken
P
,
Dubowitz
LM
.
The spectrum of leukomalacia using cranial ultrasound
.
Behav Brain Res
.
1992
;
49
(
1
):
1
6
50
International Committee for the Classification of Retinopathy of Prematurity
.
The International Classification of Retinopathy of Prematurity revisited
.
Arch Ophthalmol
.
2005
;
123
(
7
):
991
999
51
Aladangady
N
,
McHugh
S
,
Aitchison
TC
,
Wardrop
CAJ
,
Holland
BM
.
Infant’s blood vol in a controlled trial of placental transfusion at preterm delivery
.
Pediatrics
.
2006
;
117
:
93
98
52
Armanian
AM
,
Ghasemi Tehrani
H
,
Ansari
M
,
Ghasemi
S
.
Is “delayed umbilical cord clamping” beneficial for premature newborns?
Int J Pediatr
.
2017
;
5
:
4909
4918
53
Backes
CH
,
Huang
H
,
Iams
JD
,
Bauer
JA
,
Giannone
PJ
.
Timing of umbilical cord clamping among infants born at 22 through 27 weeks’ gestation
.
J Perinatol
.
2016
;
36
(
1
):
35
40
54
Baenziger
O
,
Stolkin
F
,
Keel
,
M
, et al.
The influence of the timing of cord clamping on postnatal cerebral oxygenation in preterm neonates: a randomized, controlled trial
.
Pediatrics
2007
;
119
:
455
459
55
Das
B
,
Sundaram
V
,
Kumar
P
,
Mordi
WT
,
Dhaliwal
LK
,
Das
R
.
Effect of placental transfusion on iron stores in moderately preterm neonates of 30–33 weeks gestation
.
Indian J Pediatr
.
2018
;
85
(
3
):
172
178
56
Dipak
KN
,
Nanavati
RN
,
Kabra
NK
,
Srinivasan
A
,
Ananthan
A
.
Effect of delayed cord clamping on hematocrit, and thermal and hemodynamic stability in preterm neonates: A randomized controlled trial
.
Indian P
.
2017
;
54
(
2
):
112
115
57
Dong
XY
,
Sun
XF
,
Li
MM
,
Yu
ZB
,
Han
SP
.
Influence of delayed cord clamping on preterm infants with a gestational age of <32 weeks [in Chinese]
.
Zhongguo Dang Dai Er Ke Za Zhi
.
2016
;
18
(
7
):
635
638
58
Duley
L
,
Dorling
J
,
Pushpa-Rajah
A
, et al.;
Cord Pilot Trial Collaborative Group
.
Randomised trial of cord clamping and initial stabilisation at very preterm birth
.
Arch Dis Child Fetal Neonatal Ed
.
2018
;
103
(
1
):
F6
F14
59
Gokmen
Z
,
Ozkiraz
S
,
Tarcan
A
,
Kozanoglu
I
,
Ozcimen
EE
,
Ozbek
N
.
Effects of delayed umbilical cord clamping on peripheral blood hematopoietic stem cells in premature neonates
.
J Perinat Med
.
2011
;
39
:
323
329
60
Hofmeyr
GJ
,
Bolton
KD
,
Bowen
DC
,
Govan
JJ
.
Periventricular/intraventricular haemorrhage and umbilical cord clamping
.
S Afr Med
.
1988
;
73
:
104
106
61
Hofmeyr
GJ
,
Gobetz
L
,
Bex
PJM
, et al
.
Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping: a randomized trial
.
Online J Curr Clin Trials
.
1993
;Doc No 110
62
Kinmond
S
,
Aitchison
TC
,
Holland
BM
,
Jones
JG
,
Turner
TL
,
Wardrop
CA
.
Umbilical cord clamping and preterm infants: a randomised trial
.
BMJ
.
1993
;
306
:
172
175
63
Kugelman
A
,
Borenstein-Levin
L
,
Riskin
A
, et al
.
Immediate versus delayed umbilical cord clamping in premature neonates born <35 weeks: a prospective, randomized, controlled study
.
Am J Perinatol
.
2007
;
24
:
307
315
64
McDonnell
M
,
Henderson Smart
DJ
.
Delayed umbilical cord clamping in preterm infants: a feasibility study
.
J Paediatr Child Health
.
1997
;
33
(
4
):
308
310
65
Mercer
JS
,
McGrath
MM
,
Hensman
A
,
Silver
H
,
Oh
W
.
Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial
.
J Perinatol
.
2003
;
23
:
466
472
66
Mercer
JS
,
Vohr
BR
,
Erickson-Owens
DA
,
Padbury
JF
,
Oh
W
.
Seven-month developmental outcomes of very low birth weight infants enrolled in a randomized controlled trial of delayed versus immediate cord clamping
.
J Perinatol
.
2010
;
30
(
1
):
11
16
67
Oh
W
,
Fanaroff
AA
,
Carlo
WA
, et al
.
Effects of delayed cord clamping in very-low-birth weight infants
.
J Perinatol
.
2011
;
31
:
S68
S71
68
Rabe
H
,
Wacker
A
,
Hulskamp
G
, et al
.
A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants
.
Eur J Pediatr
.
2000
;
159
(
10
):
775
777
69
Rana
A
,
Agarwal
K
,
Ramji
S
,
Gandhi
G
,
Sahu
L
.
Safety of delayed umbilical cord clamping in preterm neonates of less than 34 weeks of gestation: a randomized controlled trial
.
Obstet Gynecol Sci
.
2018
;
61
(
6
):
655
661
70
Alan
S
,
Arsan
S
,
Okulu
E
, et al
.
Effects of umbilical cord milking on the need for packed red blood cell transfusions and early neonatal hemodynamic adaptation in preterm infants born ≤1500 g: a prospective, randomized, controlled trial
.
J Pediatr Hematol Oncol
.
2014
;
36
(
8
):
e493
e498
71
Elimian
A
,
Goodman
J
,
Escobedo
M
,
Nightingale
L
,
Knudtson
E
,
Williams
M
.
Immediate compared with delayed cord clamping in the preterm neonate
.
Obstet Gynecol
.
2014
;
124
(
6
):
1075
1079
72
El-Naggar
W
,
Simpson
D
,
Hussain
A
, et al
.
The effect of umbilical cord milking on hemodynamic status of preterm infants: a randomized controlled trial
.
J Paediatr Child Health
.
2016
;
21
:
e88
73
Hosono
S
,
Mugishima
H
,
Fujita
H
, et al
.
Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born less than 29 weeks’ gestation: a randomized controlled trial
.
Arch Dis Child Fetal Neonatal Ed
.
2008
;
93
:
F14
F19
74
Katheria
A
,
Blank
D
,
Rich
W
,
Finer
N
.
Umbilical cord milking improves transition in premature infants at birth
.
Plos One
.
2014
;
9
(
4
):
e94085
75
Katheria
AC
,
Leone
TA
,
Woelkers
D
,
Garey
DM
,
Rich
W
,
Finer
NN
.
The effects of umbilical cord milking on hemodynamics and neonatal outcomes in premature neonates
.
J Pediatr
.
2014
;
164
(
5
):
1045
1050
76
Kilicdag
H
,
Gulcan
H
,
Hanta
D
, et al
.
Is umbilical cord milking always an advantage?
J Matern Fetal Neonatal Med
.
2016
;
29
(
4
):
615
618
77
March
MI
,
Hacker
MR
,
Parson
AW
,
Modest
AM
,
De
M
.
The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial
.
J Perinatol
.
2013
;
33
(
10
):
763
767
78
Ram Mohan
G
,
Shashidhar
A
,
Chandrakala
BS
,
Nesargi
S
,
Suman Rao
PN
.
Umbilical cord milking in preterm neonates requiring resuscitation: a randomized controlled trial
.
Resuscitation
.
2018
;
130
:
88
91
79
Katheria
AC
,
Truong
G
,
Cousins
L
,
Oshiro
B
,
Finer
NN
.
Umbilical cord milking versus delayed cord clamping in preterm infants
.
Pediatrics
.
2015
;
136
(
1
):
61
69
80
Krueger
MS
,
Eyal
FG
,
Peevy
KJ
,
Hamm
CR
,
Whitehurst
RM
,
Lewis
DF
.
Delayed cord clamping with and without cord stripping: a prospective randomized trial of preterm neonates
.
Am J Obstetr Gynecol
.
2015
;
212
(
3
):
394.e1

Competing Interests

POTENTIAL CONFLICT OF INTEREST: Ms Seidler is the chair of the individual participant data on Cord Management at Preterm Birth (iCOMP) Collaboration, a meta-analysis on cord clamping management using individual participant data. Dr Duley was chief investigator for the Cord Pilot Trial, collaborator for Australian Placental Transfusion Study, and a member of the secretariat for individual participant data on Cord Management at Preterm Birth. She was awarded a National Institute for Health Research grant for applied research for a program of work on care at very preterm birth, which included the Cord Pilot Trial. Ms Gyte was an investigator for the Cord Pilot Trial. Prof Rabe is the main author for 2 included studies in this review. In the event that an author of this review was also an author on an included study, that author did not assess eligibility, extract data, or assess risk of bias for the study on which he or she was an author. Dr Soll and Ms Ovelman work in the editorial office for Cochrane Neonatal, which received a contract from the American Heart Association as a Knowledge Synthesis Unit to undertake this systematic review for International Liaison Committee on Resuscitation. Dr Soll was a collaborator for the Australian Placental Transfusion Study; the other authors have indicated they have no potential conflicts of interest to disclose.

FINANCIAL DISCLOSURE: The following authors received payment from the American Heart Association, on behalf of the International Liaison Committee on Resuscitation to complete this systematic review: Ms Gyte, Prof Rabe, and Drs Díaz-Rossello and Duley received honorariums as expert systematic reviewers for the Knowledge Synthesis Unit; Ms Seidler received payment as research associate with the Knowledge Synthesis Unit; Ms Ovelman and Dr Soll are employees of the Vermont Oxford Network; the other authors have indicated they have no financial relationships relevant to this article to disclose.

Supplementary data