F1 Nutchayavaree/F2 Nachapol

October 19^th, 2020

Objective

• To compare the effects of umbilical cord milking (UCM) versus delayed cord clamping (DCC) on term infants.

Introduction

• In term infants, delayed cord clamping (DCC) has been shown to improve hematological status without complications compared with immediate cord clamping (ICC)

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• WHO, American College of Obstetricians and Gynecologists, and American Academy of Pediatrics recommend that DCC should be applied in healthy term infants

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• One study reports that umbilical cord milking (UCM) provides a placental transfusion without postponing resuscitation, and therefore, may be more beneficial than DCC

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• Since it is important to avoid iron deficiency in term and preterm infants, evaluating which placental transfusion is the best method, even in term infants, is a worthwhile endeavor.

Materials and Methods

• A systematic review of RCT according to the Cochrane Handbook for Systematic Reviews of Interventions

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• The protocol was registered and adhered to the guidelines written in the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” statement

Inclusion criteria

• All RCTs comparing UCM (intervention) to DCC were considered.

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• The keywords included “umbilical cord milking (UCM),” “delayed cord clamping (DCC),” and “term infants.”

Search strategy

• CENTRAL via Cochrane Library, EMBASE and MEDLINE via Ovid, CINAHL Plus via EBSCOhost, Web of Science Core Collection via Clarivate Analytics, and clinicaltrials.gov
• On October 27^th, 2018
• No date/time, language, document type, or publication status limitations

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Identification of studies

• An information specialist conducted the searches
• The reviewers manually conducted supplemental searches
• No language restrictions
• In cases of unpublished or ongoing trials, the authors of the studies were contacted for further information
• Four authors (KF, NT, RO, and NN) independently assessed the studies identified in the search for additional review.

Identification of studies

• Disagreements were resolved through discussion between the four authors or by consultation with a third assessor (NY, EO, and FN).
• The reviewers used piloted data extraction forms to collect basic study information and details on the participants, control interventions, treatments, and outcomes.

Data analysis

• Primary outcomes: anemia, serum ferritin, and anthropometry at 1 year of life.
• Secondary outcomes:

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1. Initial Hct level
2. Hb level at birth
3. Hb level at 6 weeks of life
4. Serum bilirubin level at 48 h of life
5. Serum ferritin level at 6 weeks of life
6. Mean blood pressure

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7. Heart rate
8. Respiratory rate
9. Body temperature
10. Any jaundice
11. NICU admission for phototherapy
12. Cranial Doppler indices measured in the MCA

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Data analysis

• Differences in dichotomous data were expressed as risk ratios
• Differences in continuous data were expressed as weighted mean differences (MDs) or standardized MDs
• A random effects meta-analysis was also conducted, and the results were presented as the average intervention effect with 95% confidence intervals (CIs).
• Statistical heterogeneity was estimated using the I² test.

- I² > 75% = substantial heterogeneity

- I² 30–60% = moderate heterogeneity

• If there were only a few studies present or if the sample size was small, a fixed-effect model was used instead because random effects models provide poor estimates of the intervention effects distribution.

Assessment of bias risk in included studies

• Four review authors (KF, NT, RO, and NN) independently assessed the risk of bias for each of the included studies using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions

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• Any disagreement was resolved through discussion between reviewers or by consultation with a third assessor (NY, EO, and FN)

Quality of evidence (GRADE)

• The quality of evidence was assessed according to the GRADE’s five downgraded criteria:
• risk of bias,
• inconsistency,
• indirectness,
• imprecision, and
• publication bias

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• The ratings were classified as high, moderate, low, or very low quality of evidence according to the four levels of quality recommended by the GRADE approach

Results: Initial results of the search

Results: Included studies

Results:

Results:

Risk of bias: authors’ judgement

Risk of bias: authors’ judgement

Quality of evidence (GRADE)

Effects of the interventions

Effects of the interventions

Discussion

• UCM may be associated with a higher Hb level at 6 weeks of life compared with DCC.
• Jaiswal et al. and Yadav et al. cut a cord at 25 cm segment
• Alzaree et al. referred to no definition of UCM
• Thus, even the UCM method remains inconsistent for each study.
• Although the mean difference of hemoglobin at 6 weeks of life was 0.17 g/dl and subtle, the difference might be greater when using an ideal UCM method.
• Progress in future studies regarding longer segments or intact cord milking is expected.

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Discussion

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• A recent meta-analysis revealed that caesarean deliveries at term were associated with a higher placental residual volume compared with vaginal deliveries because the anesthetic and surgical interventions interfered with the active contraction of uterine muscles to expel the placenta. Therefore, UCM should ideally be studied per delivery mode.

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Discussion

• Limitations
• Few high quality RCTs comparing UCM with DCC in term infants.
• The sample sizes of the three outcomes were small
• The study by Alzaree et al. had many unclear risks in terms of evaluation on risk of bias.
• the studies by Jaiswal et al. and Yadav et al. required careful interpretation of the results especially those that had large CIs.

Conclusion

• Low certainty of evidence for increased Hb levels at 6 weeks of life with UCM

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• Unable to compare UCM with DCC in terms of primary outcomes due to not enough sufficient evidence to indicate whether one technique resulted in better outcomes than the other.

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• Further research into this topic is needed in the future to gain insight into which technique is more favorable.