The Effects of Delayed Cord Clamping on 12-Month Brain Myelin Content and Neurodevelopment: A Randomized Controlled Trial

Abstract

Objective This study aimed to determine if delayed cord clamping (DCC) affected brain myelin water volume fraction (VFm) and neurodevelopment in term infants. Study Design This was a single-blinded randomized controlled trial of healthy pregnant women with term singleton fetuses randomized at birth to either immediate cord clamping (ICC) (≤ 20 seconds) or DCC (≥ 5 minutes). Follow-up at 12 months of age consisted of blood work for serum iron indices and lead levels, a nonsedated magnetic resonance imaging (MRI), followed within the week by neurodevelopmental testing. Results At birth, 73 women were randomized into one of two groups: ICC (the usual practice) or DCC (the intervention). At 12 months, among 58 active participants, 41 (80%) had usable MRIs. There were no differences between the two groups on maternal or infant demographic variables. At 12 months, infants who had DCC had increased white matter brain growth in regions localized within the right and left internal capsules, the right parietal, occipital, and prefrontal cortex. Gender exerted no difference on any variables. Developmental testing (Mullen Scales of Early Learning, nonverbal, and verbal composite scores) was not significantly different between the two groups. Conclusion At 12 months of age, infants who received DCC had greater myelin content in important brain regions involved in motor function, visual/spatial, and sensory processing. A placental transfusion at birth appeared to increase myelin content in the early developing brain. Key Points

Does Delayed Cord Clamping Improve Long-Term (≥4 Months) Neurodevelopment in Term Babies? A Systematic Review and a Meta-Analysis of Randomized Clinical Trials

“…Four trials (15,(17)(18)(19) used the same tool for neurological assessment, the Ages and Questionnaire series, and on this basis, they were included in the present meta-analysis. Four trials (16,(20)(21)(22) of T1 and T2) that was able to determine the myelin content in the brain (20,21). The characteristics of the RCTs deemed relevant for this systematic review are summarized in Table 1.…”

“…All the included studies except one were single blinded RCTs (15)(16)(17)(19)(20)(21)(22). In the remaining RCT the information about blinding was not completely clear (18).…”

“…In the remaining RCT the information about blinding was not completely clear (18). However, as clearly stated in many studies (15)(16)(17)22), the mother could not be blinded as well as the personal attending the birth (15)(16)(17)(19)(20)(21)(22). The methodological quality of the trials was addressed by adopting the Cochrane collaboration's tool for assessing the risk of bias: Figures 1B,C, respectively, report the detailed scores and the overall summary.…”

“…The results of this meta-analysis suggest a positive impact of the extra blood volume received by infants in the first minutes after birth on cognitive and behavioral skills, evaluated through ASQ at 12 months of life. However, two studies by Mercer et al (20,21), not included in the quantitative analysis, measured with a novel MRI technique the myelin content in infants exposed to placental transfusion at 4 and 12 months, respectively. These studies (20,21) found not only that infants whose cord was clamped and cut after 5 min had an enhanced myelin formation in their brain, but also that this higher content of myelin was likely due to their larger iron stores, facilitated by placental transfusion.…”

“…This blinding system could have influenced the scores obtained when parents were involved in compiling the questionnaires to assess their infants' neurodevelopment. However, although this is true for questionnaires like ASQ, presumably, it is not valid for the objective cerebral MRI assessment performed by Mercer et al (20,21). Second, due to the limited number of studies included in the quantitative synthesis, the publication bias was assessed only by funnel plots (12).…”