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Original Investigation |

Effect of Delayed Cord Clamping on Neurodevelopment at 4 Years of Age A Randomized Clinical Trial

Ola Andersson, MD, PhD1; Barbro Lindquist, PhD2; Magnus Lindgren, PhD3; Karin Stjernqvist, PhD3; Magnus Domellöf, MD, PhD4; Lena Hellström-Westas, MD, PhD1
[+] Author Affiliations
1Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
2The Habilitation Center, Hospital of Halland, Halmstad, Sweden
3Department of Psychology, Lund University, Lund, Sweden
4Department of Clinical Sciences, Unit for Pediatrics, Umeå University, Umeå, Sweden
JAMA Pediatr. 2015;169(7):631-638. doi:10.1001/jamapediatrics.2015.0358.
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Importance  Prevention of iron deficiency in infancy may promote neurodevelopment. Delayed umbilical cord clamping (CC) prevents iron deficiency at 4 to 6 months of age, but long-term effects after 12 months of age have not been reported.

Objective  To investigate the effects of delayed CC compared with early CC on neurodevelopment at 4 years of age.

Design, Setting, and Participants  Follow-up of a randomized clinical trial conducted from April 16, 2008, through May 21, 2010, at a Swedish county hospital. Children who were included in the original study (n = 382) as full-term infants born after a low-risk pregnancy were invited to return for follow-up at 4 years of age. Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III) and Movement Assessment Battery for Children (Movement ABC) scores (collected between April 18, 2012, and July 5, 2013) were assessed by a blinded psychologist. Between April 11, 2012, and August 13, 2013, parents recorded their child’s development using the Ages and Stages Questionnaire, Third Edition (ASQ) and behavior using the Strengths and Difficulties Questionnaire. All data were analyzed by intention to treat.

Interventions  Randomization to delayed CC (≥180 seconds after delivery) or early CC (≤10 seconds after delivery).

Main Outcomes and Measures  The main outcome was full-scale IQ as assessed by the WPPSI-III. Secondary objectives were development as assessed by the scales from the WPPSI-III and Movement ABC, development as recorded using the ASQ, and behavior using the Strengths and Difficulties Questionnaire.

Results  We assessed 263 children (68.8%). No differences were found in WPPSI-III scores between groups. Delayed CC improved the adjusted mean differences (AMDs) in the ASQ personal-social (AMD, 2.8; 95% CI, 0.8-4.7) and fine-motor (AMD, 2.1; 95% CI, 0.2-4.0) domains and the Strengths and Difficulties Questionnaire prosocial subscale (AMD, 0.5; 95% CI, >0.0-0.9). Fewer children in the delayed-CC group had results below the cutoff in the ASQ fine-motor domain (11.0% vs 3.7%; P = .02) and the Movement ABC bicycle-trail task (12.9% vs 3.8%; P = .02). Boys who received delayed CC had significantly higher AMDs in the WPPSI-III processing-speed quotient (AMD, 4.2; 95% CI, 0.8-7.6; P = .02), Movement ABC bicycle-trail task (AMD, 0.8; 95% CI, 0.1-1.5; P = .03), and fine-motor (AMD, 4.7; 95% CI, 1.0-8.4; P = .01) and personal-social (AMD, 4.9; 95% CI, 1.6-8.3; P = .004) domains of the ASQ.

Conclusions and Relevance  Delayed CC compared with early CC improved scores in the fine-motor and social domains at 4 years of age, especially in boys, indicating that optimizing the time to CC may affect neurodevelopment in a low-risk population of children born in a high-income country.

Trial Registration  clinicaltrials.gov Identifier: NCT01581489

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Figure 1.
CONSORT Flow Diagram

Flowchart depicting the selection of children randomized to either early or delayed cord clamping at birth and the following attrition of study participants until the 4-year follow-up.

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Figure 2.
Proportion of Children With a Neurodevelopmental Score Below the Normal Range at 48 Months of Age

Children were assessed using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), Movement Assessment Battery for Children (ABC), and Ages and Stages Questionnaire (ASQ). Children were randomized to delayed umbilical cord clamping (CC) (≥180 seconds after delivery) or early CC (≤10 seconds after delivery). P values were calculated using logistic regression analysis and adjusted for the mother’s educational level, father’s educational level, and child’s age at testing (see also eTable 2 in Supplement 2).

aP = .06 for boys who received delayed CC vs boys who received early CC.

bP = .008 for boys who received delayed CC vs boys who received early CC.

cP = .03 for boys who received delayed CC vs boys who received early CC.

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