Evaluating Cognitive Effects
of Delayed Cord Clamping
on Early Neurological
Development
By Dr. Priyanka Nair, MD and Dr. Natalli Bertolotti, MD
Learning Objectives
 Introduce the concept of PICO
 To critically analyze an article using the PICO method
 Introduce critical appraisal of RCTs
 Discuss benefits and limitations of this RCT
Stages of EBP
1. Identification of clinical problem
2. Formulation of a relevant and specific clinical question
Systematic review
3. Search of scientific evidence
4. Evaluation of available evidence
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5. Evaluation of clinical applicability of evidence
6. Implementation of evidence in the patient care
7. Evaluation of the changing results.
What is PICO?
 PICO represents an acronym
for Patient, Intervention,
Comparison and Outcome.
 PICO is used to create a
researchable question based
on a clinical situation you
have encountered.
 Based on your PICO question,
you will identify Keywords
&/or subject terms to use in
database searches.
Santos CMC, Pimenta CAM, Nobre MRC. The PICO strategy for the research question
construction and evidence search. Rev Latino-am Enfermagem 2007 maio-junho;
15(3):508-11
.
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P: Infants
I: Delayed cord clamping
C: Immediate cord clamping
O: enhanced myelin
formation due to increased
ferritin content
Study Designs
Things to consider
The type of study
Q1. What was the aim of the study?
 To simply describe a population (PO
questions) descriptive
 To quantify the relationship between factors
(PIC/PECO) questions) analytic.
Q2. If analytic, was the intervention randomly allocated?
 Yes? RCT
 No? Observational study
Q3. When were the outcomes determined?
 Some time after the exposure or intervention? cohort
study (‘prospective study’)
 At the same time as the exposure or intervention?
cross sectional study or survey
 Before the exposure was determined? case-control
study (‘retrospective study’ based on recall of the
exposure)
Randomized Controlled Trial
An experimental comparison study in which participants are allocated to
treatment/intervention or control/placebo groups using a random mechanism. Best for
study the effect of an intervention.
Advantages:
 unbiased distribution of confounders;
 blinding more likely;
 randomization facilitates statistical analysis.
Disadvantages:
 expensive: time and money;
 volunteer bias;
 ethically problematic at times
Study Question
They hypothesized that infants born at term exposed to
placental transfusion via DCC (or cord milking) would
have greater iron stores and enhanced myelin
formation showing increased myelin content at 4
months of age compared with infants who were
exposed to ICC
Patient Population
Mercer JS, Erickson-Owens DA,Collins J, Barcelos MO, Parker AB, Padbury JF. Effects of
delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in
term infants: a randomized controlled trial. J Perinatol 2017;37:260-4.
Patient Population
Intervention
• There were 4 separate data collection
points for the subjects at 4 months of
age: well-baby visit, blood draw for iron
indices (including ferritin), MRI, and
neurodevelopmental testing.
• At 4 months, a heel capillary blood
sample was collected for a complete
blood count and iron indices including
ferritin.
• Within 1 week of the blood draw, MRI
scans were completed.
• Neurodevelopmental testing was
completed within 1 week of a
successful MRI.
Comparison
Comparison
Image Analysis
Associations between VFm and 4-month blood ferritin levels were evaluated at each
image voxel using a general linear model (GLM)
Outcome
 Despite the findings of greater ferritin levels in the DCC group at 4 months,
there were no differences in the hemoglobin and hematocrit levels
 Findings show that infants who received a placental transfusion have increased
myelin content at 4 months of age compared with infants who received ICC,
adding to a growing number of studies that describe the benefits of DCC.
 The present study examined neurodevelopmental outcomes in infants at 4
months of age as this stage of infancy marks the onset of the most rapid period of
myelin development. They observed no neurodevelopmental differences between
the DCC and ICC groups at this early time.
Questions on critical appraisal of RTCs
RCT Flowchart
Discussion
 What is the importance of iron in neurodevelopment? Oligodendrocytes, the most metabolically active cells in the
brain require iron for maturation and function.
 Myelin-producing oligodendrocytes (the predominant cell type containing iron) are composed of a mixture of ferritin
subunits, allowing them to both use and store iron in the biosynthesis of cholesterol and lipids for myelin production.
 In infants who received DCC vs ICC, this was supported by increased myelin content (evidenced by VFm) viewed on
MRI scans in brain regions important for motor and sensory processing (i.e. internal capsule) suggestive of early
development of those regions
 Findings associating VFm and blood ferritin has not been reported previously
 Neurocognitive effects of increased myelination do not present until 1-2 years. Thus, infants will return for MRI scans
and neurodevelopmental testing at 12 and 24 months of age to continue to evaluate long term outcomes of
placental transfusion
 Overall, DCC has been shown beneficial to infant’s health and nutritional outcomes based on multiple studies but its
applicability is debatable based on the power and characteristics of the study population included.
Overall, was this
a good study?
Limitations vs Benefits
Limitations
Benefits
 Low power of the study
 Interesting topic
 Partial blinding of the study
 Adds to a growing number of
studies supporting the benefits of
DCC
 Homogenous demographics (only
white participants)
 Long-term outcomes unable to
be determined
 Unable to determine
neurocognitive effects at 4
months of age
 Findings associating VFm and
blood ferritin has not been
reported previously
What could have been done better?
 Including more participants to increase power of the study
 Participant diversity
 Conducting a Meta-analysis
References
 Mercer, J. S., Erickson-Owens, D. A., Deoni, S. C., Dean, D. C., Collins, J.,
Parker, A. B., . . . Padbury, J. F. (2018). Effects of Delayed Cord Clamping on
4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A
Randomized Controlled Trial. The Journal of Pediatrics,203.
doi:10.1016/j.jpeds.2018.06.006
 Santos, C. M., Pimenta, C. A., & Nobre, M. R. (2007). The PICO strategy for
the research question construction and evidence search. Revista LatinoAmericana De Enfermagem,15(3), 508-511. doi:10.1590/s010411692007000300023
 Levin, R. (2009). Faculty Opinions recommendation of How to critically
appraise an article. Faculty Opinions – Post-Publication Peer Review of the
Biomedical Literature. doi:10.3410/f.1164776.626593
Thank you!
• Special thanks to Dr. Alperstein and our lovely chiefs
Dr. Susan Gutierrez and Dr. Julia Berg