Effects of Delayed Cord Clamping on 4-Month Ferritin Levels, Brain Myelin Content, and Neurodevelopment: A Randomized Controlled Trial

Judith S Mercer, Debra A Erickson-Owens, Sean C L Deoni, Douglas C Dean 3rd, Jennifer Collins, Ashley B Parker, Meijia Wang, Sarah Joelson, Emily N Mercer, James F Padbury, Judith S Mercer, Debra A Erickson-Owens, Sean C L Deoni, Douglas C Dean 3rd, Jennifer Collins, Ashley B Parker, Meijia Wang, Sarah Joelson, Emily N Mercer, James F Padbury

Abstract

Objective: To evaluate whether placental transfusion influences brain myelination at 4 months of age.

Study design: A partially blinded, randomized controlled trial was conducted at a level III maternity hospital in the US. Seventy-three healthy term pregnant women and their singleton fetuses were randomized to either delayed umbilical cord clamping (DCC, >5 minutes) or immediate clamping (ICC, <20 seconds). At 4 months of age, blood was drawn for ferritin levels. Neurodevelopmental testing (Mullen Scales of Early Learning) was administered, and brain myelin content was measured with magnetic resonance imaging. Correlations between myelin content and ferritin levels and group-wise DCC vs ICC brain myelin content were completed.

Results: In the DCC and ICC groups, clamping time was 172 ± 188 seconds vs 28 ± 76 seconds (P < .002), respectively; the 48-hour hematocrit was 57.6% vs 53.1% (P < .01). At 4 months, infants with DCC had significantly greater ferritin levels (96.4 vs 65.3 ng/dL, P = .03). There was a positive relationship between ferritin and myelin content. Infants randomized to the DCC group had greater myelin content in the internal capsule and other early maturing brain regions associated with motor, visual, and sensory processing/function. No differences were seen between groups in the Mullen testing.

Conclusion: At 4 months, infants born at term receiving DCC had greater ferritin levels and increased brain myelin in areas important for early life functional development. Endowment of iron-rich red blood cells obtained through DCC may offer a longitudinal advantage for early white matter development.

Trial registration: ClinicalTrials.gov: NCT01620008.

Keywords: delayed cord clamping; iron; myelin; placental transfusion; umbilical cord milking.

Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 2
Figure 2
Correlation between myelin and ferritin at 4 months of age. Significance is indicated by the color scale on the right with yellow at P value of .01 and red indicating .05.
Figure 3
Figure 3
Group differences in myelin content between infants with DCC vs ICC by actual treatment. Significance is indicated by the color scale on the right with yellow at P value of .01 and red at a P value of .05. These colors represent areas in which myelin is greater in infants who had DCC compared with those who had ICC.
Figure 1
Figure 1
Infant brain study 4-month randomized cohort flowchart.

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