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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials

EK Hutton and ES Hassan.

Review published: 2007.

Link to full article: [Journal publisher]

CRD summary

The review evaluated the benefits and harms of late versus early cord clamping in term infants. The authors concluded that delayed clamping is beneficial to the newborn and benefits extend into infancy, although polycythaemia increases. Overall, this was a well-conducted review and the conclusions appear reliable.

Authors' objectives

To evaluate the benefits and harms of late versus early cord clamping in term infants.

Searching

MEDLINE, EMBASE, CINHAL, the Cochrane Library, the Cochrane Pregnancy and Childbirth Group's Specialised Register and the Cochrane Neonatal Group's Specialised Register were searched from inception to November 2006 without any language restrictions; the search terms were reported. In addition, references of relevant studies were screened and pertinent researchers were contacted for further unpublished research.

Study selection

Study designs of evaluations included in the review

Controlled studies were eligible, both randomised controlled trials (RCTs) and non-randomised clinical trials (CTs).

Specific interventions included in the review

Studies comparing early versus late cord clamping following birth were eligible for inclusion. The included studies described early clamping within the first 10 or 60 seconds, immediately or as soon as possible after delivery, with the majority using the 10 seconds definition; late clamping was described as 1, 2 or 5 minutes after birth or after descent of the placenta in the vagina, but primarily as 3 minutes after birth or after cessation of cord pulsations. The studies were conducted in countries with low (less than 10 per 1,000 total births), moderate (10 to 20) and higher (more than 20) perinatal mortality rates.

Participants included in the review

Studies with infants born at 37 or more weeks' gestation by vaginal or Caesarean delivery were eligible for inclusion. Studies with only pre-term infants or low birth weight infants were excluded. The included studies specified various inclusion and exclusion criteria; the majority included only singleton term infants born after uneventful pregnancies or deliveries. Overall, approximately 2.7% infants were delivered by Caesarean section.

Outcomes assessed in the review

Studies had to report at least one of a list of a priori-specified indicators for benefits or harms for neonates. Such indicators included reported or clinically determined jaundice, use of phototherapy and polycythaemia (defined as haematocrit increased to more than 65%).

How were decisions on the relevance of primary studies made?

Two reviewers independently assessed the studies.

Assessment of study quality

Two reviewers independently assessed the trials on a modified Jadad scale; trials rated 10 or more were considered high quality. Any disagreements were resolved through consensus.

Data extraction

The data were extracted in duplicate and any differences were resolved through consensus. The reported mean and standard deviation were extracted for continuous variables. Data on harms were extracted to compute the relative risk (RR) of adverse events.

Methods of synthesis

How were the studies combined?

Weighted mean differences (WMDs) or pooled RRs were computed using fixed-effect models; random-effects models were used in the presence of statistical heterogeneity. Data on intermediary clamping timeframe (at 1 minute) were excluded from the analyses.

How were differences between studies investigated?

Statistical heterogeneity was assessed using the chi-squared test and the I-squared statistic (I-squared values of more than 50% were considered heterogeneous). Sensitivity analyses investigating study quality and planned subgroup analyses were also conducted.

Results of the review

Fifteen studies (n=2,021, of whom 1,912 were considered for meta-analysis) were included in the review. There were 8 RCTs (n=1,719) and 7 CTs (n=302).

Six RCTs were rated 10 or higher quality. The majority of CTs scored 7 on the quality scale.

Late clamping was associated with a significant increase in haematocrit at 6 hours (WMD 4.16%, 95% CI: 0.83, 7.49; 2 studies, n=494), 24 to 48 hours (WMD 10.01%, 95% CI: 4.10, 15.92; 4 studies, n=341), 5 days (WMD 11.97%, 95% CI: 8.50, 15.45; 4 studies, n=120) and 2 months (WMD 3.70, 95% CI: 2.00, 5.40; 1 study, n=47), but not 6 months after delivery (WMD 0.10%, 95% CI: -0.62, 0.82; 1 study, n=305). Late clamping was associated with a significantly increased ferritin concentration 2 or 3 months after delivery (WMD 17.89 mg/L, 95% CI: 16.58, 19.21; 2 studies, n=144) and a significant increase in stored iron measurements in 6-months-olds (WMD 19.90, 95% CI: 7.67, 32.13; 1 study, n=315).

Late clamping was associated with a significant and clinically important reduction in the risk of anaemia at 2 or 3 months (RR 0.53, 95% CI: 0.40, 0.70; 2 studies, n=119) compared with early clamping, but there was no significant difference between treatments at 6 months (1 study, n=356).

Babies with late clamping were at increased risk of experiencing asymptomatic polycythaemia at 24 to 48 hours (RR 3.82, 95% CI: 1.11, 13.21; based on 3 studies reporting at least one event).

There were no statistically significant differences between early and late clamping for tachypnoea or grunting (3 studies, n=296) or admission to neonatal intensive care units (1 study, n=185).

Authors' conclusions

The delay of clamping of the umbilical cord in full-term babies for a minimum of 2 minutes following birth is beneficial to the newborn and benefits extend into infancy. There was an increase in polycythemia among infants in whom cord clamping was delayed, however, the condition appeared benign.

CRD commentary

The review addressed a clear research question with well-defined inclusion criteria. The search was thorough, no language restrictions were applied and unpublished studies were sought, thereby reducing the risk of language and publication bias. The reviewers undertook measures throughout the review process to reduce bias and errors. The quality of the included studies was assessed and its influence investigated in sensitivity analyses. However, no details were given of modifications made to the Jadad scoring system, which was designed for use with RCTs and not CTs, and only a composite score was presented; this makes it difficult for the reader to judge the quality of the included studies.

Statistical heterogeneity was assessed and studies were appropriately combined using meta-analysis. Some included studies had small sample sizes and several outcomes were only investigated in very few studies, raising questions about the generalisability of the results. Overall, this was a well-conducted review and the conclusions appear reliable.

Implications of the review for practice and research

Practice: The authors stated that the review supports the incorporation of a minimum delay of 2 minutes before clamping the umbilical cord following birth for all full-term newborns. The results are of particular importance for developing countries in which anaemia during infancy and childhood is highly prevalent.

Research: The authors stated that research should refine the timing of clamping to determine the minimum time required to provide maximum benefit. Further research to assess the potential adverse effects of early clamping is needed.

Bibliographic details

Hutton E K, Hassan E S. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA 2007; 297(11): 1241-1252. [PubMed: 17374818]

Original Paper URL

http://jama.ama-assn.org/

Indexing Status

Subject indexing assigned by NLM

MeSH

Anemia; Constriction; Delivery, Obstetric /methods; Fetal Blood; Humans; Infant, Newborn /blood; Jaundice, Neonatal; Ligation; Polycythemia; Risk; Term Birth; Time Factors; Umbilical Cord

AccessionNumber

12007008099

Database entry date

30/11/2007

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 17374818

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