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

Judith S. Mercer; Debra A. Erickson-Owens; Sean C.L. Deoni; Douglas C. Dean III; Richard Tucker; Ashley B. Parker; Sarah Joelson; Emily N. Mercer; Jennifer Collins; James F. Padbury

doi:10.1055/s-0040-1714258

American Journal of Perinatology, Inhaltsverzeichnis

Am J Perinatol 2022; 39(01): 037-044
DOI: 10.1055/s-0040-1714258

Original Article

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

Judith S. Mercer

¹College of Nursing, University of Rhode Island, Kingston, Rhode Island

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

³Pediatrics, Alpert School of Medicine, Brown University, Providence, Rhode Island

,

Debra A. Erickson-Owens

¹College of Nursing, University of Rhode Island, Kingston, Rhode Island

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

,

Sean C.L. Deoni

⁴Advanced Baby Imaging Lab, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island

⁵Maternal, Neonatal, and Child Health, Discovery and Tools, Bill and Melinda Gates Foundation, Munirka, New Delhi, India

,

Douglas C. Dean III

⁶Department of Pediatrics, University of Wisconsin, Madison, Wisconsin

⁷Department of Medical Physics, University of Wisconsin, Madison, Wisconsin

⁸Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin, Madison, Wisconsin

,

Richard Tucker

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

,

Ashley B. Parker

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

,

Sarah Joelson

⁴Advanced Baby Imaging Lab, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island

,

Emily N. Mercer

⁴Advanced Baby Imaging Lab, Memorial Hospital of Rhode Island, Pawtucket, Rhode Island

,

Jennifer Collins

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

,

James F. Padbury

²Department of Pediatrics, Women and Infants Hospital of Rhode Island, Providence, Rhode Island

³Pediatrics, Alpert School of Medicine, Brown University, Providence, Rhode Island

› Institutsangaben

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

DCC resulted in higher hematocrits in newborn period.
DCC appears to increase myelin at 12 months.
Gender did not influence study outcomes.

Keywords

umbilical cord - iron - placental transfusion - delayed cord clamping - myelin

Volltext

Referenzen

References
1 Farrar D, Airey R, Law GR, Tuffnell D, Cattle B, Duley L. Measuring placental transfusion for term births: weighing babies with cord intact. BJOG 2011; 118 (01) 70-75
2 Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta after birth. Lancet 1969; 2 (7626): 871-873
3 Arcilla RA, Oh W, Lind J, Gessner IH. Pulmonary arterial pressures of newborn infants born with early and late clamping of the cord. Acta Paediatr Scand 1966; 55 (03) 305-315
4 Jaykka S. Capillary erection and the structural appearance of fetal and neonatl lungs. Acta Paediatr (Stockh) 1958; 47 (05) 484-500
5 Nelle M, Zilow EP, Bastert G, Linderkamp O. Effect of Leboyer childbirth on cardiac output, cerebral and gastrointestinal blood flow velocities in full-term neonates. Am J Perinatol 1995; 12 (03) 212-216
6 Oh W, Lind J. Renal function and blood volume in newborn infant related to placental transfusion. Acta Paediatr Scand 1966; 55: 197-210
7 Oh W, Lind J. Venous and capillary hematocrit in newborn infants and placental transfusion. Acta Paediatr Scand 1966; 55 (01) 38-48
8 Cernadas J, Carroli G, Pellegrini L, Otano L, Ferreira M, Ricci C. The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized controlled trial. Obstet Gynecol Surv 2006; 61 (09) 564-565
9 Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Líz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial. Lancet 2006; 367 (9527): 1997-2004
10 Andersson O, Hellström-Westas L, Andersson D, Domellöf M. Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. BMJ 2011; 343: d7157
11 Mercer JS, Erickson-Owens DA, Deoni SCL. et al. Effects of delayed cord clamping on 4-month ferritin levels, brain myelin content, and neurodevelopment: a randomized controlled trial. J Pediatr 2018; 203: 266-272.e2
12 Connor JR, Menzies SL. Relationship of iron to oligodendrocytes and myelination. Glia 1996; 17 (02) 83-93
13 Todorich B, Pasquini JM, Garcia CI, Paez PM, Connor JR. Oligodendrocytes and myelination: the role of iron. Glia 2009; 57 (05) 467-478
14 Georgieff MK. The role of iron in neurodevelopment: fetal iron deficiency and the developing hippocampus. Biochem Soc Trans 2008; 36 (Pt 6): 1267-1271
15 Georgieff MK. Iron assessment to protect the developing brain. Am J Clin Nutr 2017; 106 (Suppl. 06) 1588S-1593S
16 Lozoff B, Smith JB, Kaciroti N, Clark KM, Guevara S, Jimenez E. Functional significance of early-life iron deficiency: outcomes at 25 years. J Pediatr 2013; 163 (05) 1260-1266
17 Beard JL, Connor JR. Iron status and neural functioning. Annu Rev Nutr 2003; 23: 41-58
18 Barks A, Hall AM, Tran PV, Georgieff MK. Iron as a model nutrient for understanding the nutritional origins of neuropsychiatric disease. Pediatr Res 2019; 85 (02) 176-182
19 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 (03) 260-264
20 Deoni SCL, Dean III DC, O'Muircheartaigh J, Dirks H, Jerskey BA. Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage 2012; 63 (03) 1038-1053
21 Dean III DC, O'Muircheartaigh J, Dirks H. et al. Characterizing longitudinal white matter development during early childhood. Brain Struct Funct 2015; 220 (04) 1921-1933
22 Deoni SCL, O'Muircheartaigh J, Elison JT. et al. White matter maturation profiles through early childhood predict general cognitive ability. Brain Struct Funct 2016; 221 (02) 1189-1203
23 Deoni SCL, Zinkstok JR, Daly E, Ecker C, Williams SC, Murphy DG. MRC AIMS Consortium. White-matter relaxation time and myelin water fraction differences in young adults with autism. Psychol Med 2015; 45 (04) 795-805
24 Kitzler HH, Su J, Zeineh M. et al. Deficient MWF mapping in multiple sclerosis using 3D whole-brain multi-component relaxation MRI. Neuroimage 2012; 59 (03) 2670-2677
25 Kolind S, Matthews L, Johansen-Berg H. et al. Myelin water imaging reflects clinical variability in multiple sclerosis. Neuroimage 2012; 60 (01) 263-270
26 Dean III DC, Hurley SA, Kecskemeti SR. et al. Association of amyloid pathology with myelin alteration in preclinical Alzheimer disease. JAMA Neurol 2017; 74 (01) 41-49
27 Mullen E. Mullen Scales of Early Learning. Circle Pines, MN: American Guidance Services, Inc; 1995
28 Briggs-Gowan M, Carter A. Brief Infant Toddler Social Emotional Assessment Manual. San Antonio: Harcourt Assessment; 2006
29 Deoni SCL, Rutt BK, Jones DK. Investigating exchange and multicomponent relaxation in fully balanced steady-state free precession imaging. J Magn Reson Imaging 2008; 27 (06) 1421-1429
30 Heller R, Stanley D, Yekutieli D, Rubin N, Benjamini Y. Cluster-based analysis of FMRI data. Neuroimage 2006; 33 (02) 599-608
31 Smith SM, Jenkinson M, Woolrich MW. et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 2004; 23 (Suppl. 01) S208-S219
32 Dubois J, Dehaene-Lambertz G, Kulikova S, Poupon C, Hüppi PS, Hertz-Pannier L. The early development of brain white matter: a review of imaging studies in fetuses, newborns and infants. Neuroscience 2014; 276: 48-71
33 Cusick SE, Georgieff MK, Rao R. Approaches for reducing the risk of early-life iron deficiency-induced brain dysfunction in children. Nutrients 2018; 10 (02) E227
34 Rao R, Bora R. Timing of umbilical cord clamping and infant brain development. J Pediatr 2018; 203: 8-10
35 Cotten CM, Murtha AP, Goldberg RN. et al. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr 2014; 164 (05) 973-979.e1
36 Liao Y, Cotten M, Tan S, Kurtzberg J, Cairo MS. Rescuing the neonatal brain from hypoxic injury with autologous cord blood. Bone Marrow Transplant 2013; 48 (07) 890-900
37 Kc A, Rana N, Målqvist M, Jarawka Ranneberg L, Subedi K, Andersson O. Effects of delayed umbilical cord clamping vs early clamping on anemia in infants at 8 and 12 months: a randomized clinical trial. JAMA Pediatr 2017; 171 (03) 264-270
38 Andersson O, Domellöf M, Andersson D, Hellström-Westas L. Effect of delayed vs early umbilical cord clamping on iron status and neurodevelopment at age 12 months: a randomized clinical trial. JAMA Pediatr 2014; 168 (06) 547-554
39 Mercer JS, Erickson-Owens DA. Rethinking placental transfusion and cord clamping issues. J Perinat Neonatal Nurs 2012; 26 (03) 202-217 , quiz 218–219
40 Boere I, Roest AAW, Wallace E. et al. Umbilical blood flow patterns directly after birth before delayed cord clamping. Arch Dis Child Fetal Neonatal Ed 2015; 100 (02) F121-F125
41 Di Tommaso M, Carotenuto B, Seravalli V. et al. Evaluation of umbilical cord pulsatility after vaginal delivery in singleton pregnancies at term. Eur J Obstet Gynecol Reprod Biol 2019; 236: 94-97
42 Winkler A, Gustaffson A, Andersson O. Effects of extended delayed cord clamping on bilirubin and postpartum hemorrhage. Poster presented at: Pediatric Academic Societies; 2018; Toronto, CA
43 Kc A, Målqvist M, Rana N, Ranneberg LJ, Andersson O. ; KC A. Effect of timing of umbilical cord clamping on anaemia at 8 and 12 months and later neurodevelopment in late pre-term and term infants; a facility-based, randomized-controlled trial in Nepal. BMC Pediatr 2016; 16: 35
44 O'Muircheartaigh J, Dean III DC, Ginestet CE. et al. White matter development and early cognition in babies and toddlers. Hum Brain Mapp 2014; 35 (09) 4475-4487
45 Deoni SCL, Kolind SH. Investigating the stability of mcDESPOT myelin water fraction values derived using a stochastic region contraction approach. Magn Reson Med 2015; 73 (01) 161-169

Zusatzmaterial

Supplementary Material