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Original Investigation
January 17, 2017

Effects of Delayed Umbilical Cord Clamping vs Early Clamping on Anemia in Infants at 8 and 12 MonthsA Randomized Clinical Trial

Author Affiliations
  • 1International Maternal and Child Health, Department of Women’s and Children’s Health, Uppsala University, Uppsala, Sweden
  • 2Health Section, United Nations Children’s Fund (UNICEF), Lalitpur, Nepal
  • 3Paropakar Maternity and Women’s Hospital, Kathmandu, Nepal
  • 4Department of Pediatrics, Hospital of Halland, Halmstad, Sweden
JAMA Pediatr. Published online January 17, 2017. doi:10.1001/jamapediatrics.2016.3971
Key Points

Question  Can delaying umbilical cord clamping for 3 minutes after birth reduce anemia at 8 and 12 months of age?

Findings  In this randomized clinical trial, 540 newborns were randomized to delayed umbilical cord clamping (>3 minutes) or early clamping no later than 1 minute. This delay resulted in a significant reduction in the prevalence of anemia by 9% at 8 months or age and 8% at 12 months of age.

Meaning  By extending umbilical cord clamping to longer than 3 minutes after birth, infants in low-resource settings experience less anemia, which may have positive effects on health and development.

Abstract

Importance  Delayed umbilical cord clamping has been shown to improve iron stores in infants to 6 months of age. However, delayed cord clamping has not been shown to prevent iron deficiency or anemia after 6 months of age.

Objective  To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on hemoglobin and ferritin levels at 8 and 12 months of age in infants at high risk for iron deficiency anemia.

Design, Setting, and Participants  This randomized clinical trial included 540 late preterm and term infants born vaginally at a tertiary hospital in Kathmandu, Nepal, from October 2 to November 21, 2014. Follow-up included blood levels of hemoglobin and ferritin at 8 and 12 months of age. Follow-up was completed on December 11, 2015. Analysis was based on intention to treat.

Interventions  Infants were randomized to delayed umbilical cord clamping (≥180 seconds after delivery) or early clamping (≤60 seconds after delivery).

Main Outcomes and Measures  Main outcomes included hemoglobin and anemia levels at 8 months of age with the power estimate based on the prevalence of anemia. Secondary outcomes included hemoglobin and anemia levels at 12 months of age and ferritin level, iron deficiency, and iron deficiency anemia at 8 and 12 months of age.

Results  In this study of 540 infants (281 boys [52.0%] and 259 girls [48.0%]; mean [SD] gestational age, 39.2 [1.1] weeks), 270 each were randomized to the delayed and early clamping groups. At 8 months of age, 212 infants (78.5%) from the delayed group and 188 (69.6%) from the early clamping group returned for blood sampling. After multiple imputation analysis, infants undergoing delayed clamping had higher levels of hemoglobin (10.4 vs 10.2 g/dL; difference, 0.2 g/dL; 95% CI, 0.1 to 0.4 g/dL). Delayed cord clamping also reduced the prevalence of anemia (hemoglobin level <11.0 g/dL) at 8 months in 197 (73.0%) vs 222 (82.2%) infants (relative risk, 0.89; 95% CI, 0.81-0.98; number needed to treat [NNT], 11; 95% CI, 6-54). At 8 months, the risk for iron deficiency was reduced in the delayed clamping group in 60 (22.2%) vs 103 (38.1%) patients (relative risk, 0.58; 95% CI, 0.44-0.77; NNT, 6; 95% CI, 4-13). At 12 months, delayed cord clamping still resulted in a hemoglobin level of 0.3 (95% CI, 0.04-0.5) g/dL higher than in the early cord clamping group and a relative risk for anemia of 0.91 (95% CI, 0.84-0.98), resulting in a NNT of 12 (95% CI, 7-78).

Conclusions and Relevance  Delayed cord clamping reduces anemia at 8 and 12 months of age in a high-risk population, which may have major positive effects on infants’ health and development.

Trial Registration  clinicaltrials.gov Identifier: NCT02222805

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