Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial

Ola Andersson, Lena Hellström-Westas, Dan Andersson, Magnus Domellöf, Ola Andersson, Lena Hellström-Westas, Dan Andersson, Magnus Domellöf

Abstract

Objective: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting.

Design: Randomised controlled trial.

Setting: Swedish county hospital.

Participants: 400 full term infants born after a low risk pregnancy.

Intervention: Infants were randomised to delayed umbilical cord clamping (≥ 180 seconds after delivery) or early clamping (≤ 10 seconds after delivery).

Main outcome measures: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy.

Results: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 μg/L v 81 μg/L, P < 0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P = 0.01, relative risk reduction 0.90; number needed to treat = 20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P = 0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy.

Conclusions: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4788321/bin/ando849935.f1_default.jpg
Participant flow through study

References

    1. Van Rheenen PF, Brabin BJ. A practical approach to timing cord clamping in resource poor settings. BMJ 2006;333:954-8.
    1. Bramhagen AC, Axelsson I. Iron status of children in southern Sweden: effects of cow’s milk and follow-on formula. Acta Paediatr 1999;88:1333-7.
    1. Thane CW, Walmsley CM, Bates CJ, Prentice A, Cole TJ. Risk factors for poor iron status in British toddlers: further analysis of data from the National Diet and Nutrition Survey of children aged 1.5-4.5 years. Public Health Nutr 2000;3:433-40.
    1. Persson LA, Lundstrom M, Lonnerdal B, Hernell O. Are weaning foods causing impaired iron and zinc status in 1-year-old Swedish infants? A cohort study. Acta Paediatr 1998;87:618-22.
    1. Beard J. Recent evidence from human and animal studies regarding iron status and infant development. J Nutr 2007;137:524-30S.
    1. Carlson ES, Tkac I, Magid R, O’Connor MB, Andrews NC, Schallert T, et al. Iron is essential for neuron development and memory function in mouse hippocampus. J Nutr 2009;139:672-9.
    1. Lozoff B, Brittenham GM, Wolf AW, McClish DK, Kuhnert PM, Jimenez E, et al. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics 1987;79:981-95.
    1. McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr 2007;85:931-45.
    1. Gunnarsson BS, Thorsdottir I, Palsson G, Gretarsson SJ. Iron status at 1 and 6 years versus developmental scores at 6 years in a well-nourished affluent population. Acta Paediatr 2007;96:391-5.
    1. Thomas DG, Grant SL, Aubuchon-Endsley NL. The role of iron in neurocognitive development. Dev Neuropsychol 2009;34:196-222.
    1. Grantham-McGregor S, Ani C. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649-68S.
    1. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev 2006;64:S34-43.
    1. Szajewska H, Ruszczynski M, Chmielewska A. Effects of iron supplementation in nonanemic pregnant women, infants, and young children on the mental performance and psychomotor development of children: a systematic review of randomized controlled trials. Am J Clin Nutr 2010;91:1684-90.
    1. Sachdev H, Gera T, Nestel P. Effect of iron supplementation on mental and motor development in children: systematic review of randomised controlled trials. Public Health Nutr 2005;8:117-32.
    1. Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta after birth. Lancet 1969;2:871-3.
    1. McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev 2008;2:CD004074.
    1. Geethanath RM, Ramji S, Thirupuram S, Rao YN. Effect of timing of cord clamping on the iron status of infants at 3 months. Indian Pediatr 1997;34:103-6.
    1. Gupta R, Ramji S. Effect of delayed cord clamping on iron stores in infants born to anemic mothers: a randomized controlled trial. Indian Pediatr 2002;39:130-5.
    1. Grajeda R, Perez-Escamilla R, Dewey KG. Delayed clamping of the umbilical cord improves hematologic status of Guatemalan infants at 2 mo of age. Am J Clin Nutr 1997;65:425-31.
    1. Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Liz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial. Lancet 2006;367:1997-2004.
    1. Van Rheenen P, de Moor L, Eschbach S, de Grooth H, Brabin B. Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled trial in term babies. Trop Med Int Health 2007;12:603-16.
    1. Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA 2007;297:1241-52.
    1. Male C, Persson LA, Freeman V, Guerra A, van’t Hof MA, Haschke F. Prevalence of iron deficiency in 12-mo-old infants from 11 European areas and influence of dietary factors on iron status (Euro-Growth study). Acta Paediatr 2001;90:492-8.
    1. Looker AC, Dallman PR, Carroll MD, Gunter EW, Johnson CL. Prevalence of iron deficiency in the United States. JAMA 1997;277:973-6.
    1. Yao AC, Lind J, Vuorenkoski V. Expiratory grunting in the late clamped normal neonate. Pediatrics 1971;48:865-70.
    1. Saigal S, Usher RH. Symptomatic neonatal plethora. Biol Neonate 1977;32:62-72.
    1. Van Rheenen P, Brabin BJ. Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: a systematic review. Ann Trop Paediatr 2004;24:3-16.
    1. Winter C, Macfarlane A, Deneux-Tharaux C, Zhang WH, Alexander S, Brocklehurst P, et al. Variations in policies for management of the third stage of labour and the immediate management of postpartum haemorrhage in Europe. BJOG 2007;114:845-54.
    1. Dallman PR. Red blood cell values at various ages. In: Rudolph A, ed. Pediatrics. 16th ed. Appleton-Centrury-Crofts, 1977:1111.
    1. Pappas A, Delaney-Black V. Differential diagnosis and management of polycythemia. Pediatr Clin North Am 2004;51:1063-86.
    1. Domellöf M, Dewey KG, Lönnerdal B, Cohen RJ, Hernell O. The diagnostic criteria for iron deficiency in infants should be re-evaluated. J Nutr 2002;132:3680-6.
    1. Saarinen UM, Siimes MA. Developmental changes in serum iron, total iron-binding capacity, and transferrin saturation in infancy. J Pediatr 1977;91:875-7.
    1. Pfeiffer CM, Cook JD, Mei Z, Cogswell ME, Looker AC, Lacher DA. Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays. Clin Chim Acta 2007;382:112-6.
    1. Malope BI, MacPhail AP, Alberts M, Hiss DC. The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status. Br J Haematol 2001;115:84-9.
    1. Cook JD, Flowers CH, Skikne BS. The quantitative assessment of body iron. Blood 2003;101:3359-63.
    1. Mei Z, Cogswell ME, Parvanta I, Lynch S, Beard JL, Stoltzfus RJ, et al. Hemoglobin and ferritin are currently the most efficient indicators of population response to iron interventions: an analysis of nine randomized controlled trials. J Nutr 2005;135:1974-80.
    1. Domellof M, Cohen RJ, Dewey KG, Hernell O, Rivera LL, Lonnerdal B. Iron supplementation of breast-fed Honduran and Swedish infants from 4 to 9 months of age. J Pediatr 2001;138:679-87.
    1. Hodges JL Jr, Lehmann EL. Estimates of location based on rank tests. Ann Math Stat 1963;34:598-611.
    1. Pezzullo JC. JavaStat: 2-way contingency table analysis. .
    1. Domellof M. Iron requirements, absorption and metabolism in infancy and childhood. Curr Opin Clin Nutr Metab Care 2007;10:329-35.
    1. Yao AC, Lind J. Effect of gravity on placental transfusion. Lancet 1969;2:505-8.
    1. Nelle M, Zilow EP, Kraus M, Bastert G, Linderkamp O. The effect of Leboyer delivery on blood viscosity and other hemorheologic parameters in term neonates. Am J Obstet Gynecol 1993;169:189-93.
    1. Chantry CJ, Howard CR, Auinger P. Full breastfeeding duration and risk for iron deficiency in US infants. Breastfeed Med 2007;2:63-73.
    1. Fewtrell M, Wilson DC, Booth I, Lucas A. Six months of exclusive breast feeding: how good is the evidence? BMJ 2011;342:c5955.
    1. Ceriani Cernadas JM, Carroli G, Pellegrini L, Otano L, Ferreira M, Ricci C, et al. The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized, controlled trial. Pediatrics 2006;117:e779-86.
    1. Emhamed MO, van Rheenen P, Brabin BJ. The early effects of delayed cord clamping in term infants born to Libyan mothers. Trop Doct 2004;34:218-22.

Source: PubMed

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