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When to clamp the umbilical cord for full term babies?

December 2016
Dr. Elisabeth Semple

 

A review of the current literature comparing early and delayed clamping of the umbilical cord after term births.

During the last 20 years evidence has been accumulating about the benefits to the newborn of delayed clamping of the cord after birth. These benefits include increased iron stores and a decreased risk of anemia up to 4-6 months of age.1,2 Adequate availability of iron is important for the development of the brain during the first years of life3,4 and transferring the cord blood at birth is an easy way to elevate the ferritin in the blood of newborn. As an increasing number of parents are considering storing or donating their cord blood, is there a way to both benefit the baby and collect cord blood?  

What does “early” and “delayed” mean?

One difficulty when assessing the data is the inconsistency of the definitions of “early” and “delayed” clamping. “Early” has been defined as any time between 10 sec to 1 min, and “delayed” as between 30 sec to 5 min. 

A systematic review and meta-analysis of the available data was performed in 2006 by Hutton and Hassan1 where they compared the outcomes in 15 clinical studies of term babies.5-19 They defined “early” as within 10-15 sec of birth and “delayed” as 2 minutes or more after birth. A similar review, also on term babies, was e-published in 2013 from the Cochrane Collaboration, authored by McDonald et al.2 Several of the studies used by Hutton were included but this analysis5-12, also included studies published between 1997 and 2012, a total of 15 studies.20-25 The definition of “early” was less than 15 sec and of “delayed” was defined as more than 1 min after birth.  

What do the SOGC and ACOG say?

The SOGC (Society of Obstetricians and Gynaecologists of Canada) addressed the timing of cord clamping in their Clinical Practice Guideline, Active management of the third stage of labour: Prevention and treatment of postpartum hemorrhage, published Oct 2009.26 They recommend the following: “Whenever possible, delaying the clamping of the cord by at least 60 seconds is preferred to clamping earlier in premature newborns (<37 weeks’ gestation)….” For term babies, they recommend caution about delaying clamping due to the possible risk of increased jaundice requiring phototherapy.

The ACOG (American Congress of Obstetricians and Gynecologists) released their updated recommendation in January 2017 and they conclude27: “Term and pre-term infants appear to derive benefit from delayed umbilical cord clamping; therefore delayed umbilical cord clamping for at least 30-60 seconds is recommended in term and pre-term infants except when immediate umbilical cord clamping is necessary because of neonatal or maternal indications.”

What are the benefits of delayed clamping?

Both of the meta-analyses referred to above and most other published studies present data which show that delayed clamping gives newborns increased iron levels in their blood and a decreased risk for iron deficiency during the first months of life.1,2 However, as the authors point out, there was a large variation among the studies in how they evaluated iron deficiency, including how iron deficiency was defined.

Moreover, in the two meta-analyses, the difference in iron levels between the groups with early versus delayed clamping varies. One factor in these differences could be the iron status of the mother. Several of the studies included in the analyses were conducted in low and medium income settings (e.g. Argentina5, Mexico6, Libya7, India8,11) where the level of maternal care may not be the same as in North America. One study that was included in both meta-analyses has evaluated the influence of maternal iron levels6. They found that delayed clamping had a greater impact on newborn iron levels when the mother had low iron levels (defined as <9µg/L).

A group in Sweden has conducted the first modern-era long-term study of the impact of delayed cord clamping for term babies born in a country with rich resources.

Anderson et al.22 published a study on 400 term babies born in Sweden in 2011. In this study, they defined “early clamping” as within 15 sec of birth and “delayed clamping” as after 3 min, during which time they held the baby 20 cm below the vulva. At the follow up four months after birth, they found that the group with delayed clamping had significantly higher iron levels  (117 µ g/L versus 81 µ g/L ), and that iron deficiency was less prevalent in the delayed clamping group, but the prevalence of anemia was the same in both groups. The authors conclude that “delayed clamping, in this randomized controlled trial, resulted in improved ferritin levels and reduced the prevalence of iron deficiency at four months of age.”

The same group published follow ups on the same babies at 12 months and 4 years of age.28,31 To our knowledge, this is the first study since 194129 to look at the effects of delayed clamping beyond 6 months. After 12 months, they found that there was no longer a difference between the groups in any of the iron status indicators, nor was there a difference in the level of anemia28.

Because adequate iron levels are important for pediatric brain development, the researchers evaluated the neurodevelopment of children in the study by asking parents to answer the Ages and Stages Questionnaire (ASQ) to assess their child’s development. This tool did not find any difference between the two groups at age 12 months and there was no correlation between neurodevelopment and iron status at birth or at 4 months28.

The neurodevelopment of the same children was again followed up at 4 years of age.31 The researchers found that, for girls, the time of clamping did not make any difference in any of the tests performed. However, boys that had early cord clamping showed slightly late development in fine motor skills and social skills. Unfortunately, this study only reported on neurodevelopment, not on iron levels or nutrition (the natural way to get iron). As neurodevelopment can be influenced by many factors, not just the level of iron at birth, further research is needed on larger groups of children to ensure that this result can be confirmed.

Are there any risks with delayed clamping?

It has often been suggested that delayed cord clamping in full term infants could result in more instances of jaundice requiring light therapy, but this has not been proven with published data.2 In addition to clamping delay, there are other factors that influence the transfer of blood from the placenta to the baby. It has been suggested that focusing only on clamping delay and ignoring other factors such as when the baby starts breathing could be counter-productive for the infant and could even result in infant-to-placenta transfer of blood.33

Are there any risks with early clamping?

It is known that it is important to prevent iron deficiency in order to achieve optimal brain development.4 While all the available data show that delayed clamping will increase the iron levels, are there any data showing that early clamping results in iron levels that are too low? This analysis is complicated by the fact that the studies are using different definitions for identifying iron deficiency and low ferritin.

Table 1 below shows iron levels of early versus delayed clamping groups in the Cochrane review.2 Using blood ferritin levels as an indicator for iron deficiency, we can see that although there are significant differences between the early versus late clamping groups, none of the groups has a mean ferritin level close to the limit of low ferritin. In the study by Andersson22, 7% of the infants that had early clamping had a ferritin level <20 µ g/L, compared with none in the delayed group. However at the 12 months follow up 1% and 2% of the infants had low ferritin levels (early and delayed clamping, respectively).28

There is no reliable data so far showing that there is any impact of the timing of cord clamping on the long-term iron levels and neurodevelopment of the infants in any of the studies.

 

Table 1:

         Study

Definition: Iron deficiency

Definition:
Low Ferritin

Ferritin:
Study result at 3-6 months
mean±sd; median (range)

Al-Tawil 2012
Saudi-Arabia21

MVC <73fL
Transferrin saturation <10%

<20µg/L

Early: 228±147 µ g/L
Delayed: 430±132 µ g/L

Andersson 2011, 2014
Sweden22,28

>2 indicators outside ref. values
(ferritin<20 µ g/L, MCV <73fL,
transferrin saturation <10%,
transferrin receptors>7mg/L)

<20 µ g/L (4 m)
<12 µ g/L (12m)

At 4 months:
Early: 81 µ g/L (6-670)
Delayed: 117 µ g/L (20-880)

After 12 months:
Early: 34±0.24 µ g/L
Delayed: 35±0.22 µ g/L

Cernadas, 2010
Argentina5

Hemoglobin <105 g/L and ferritin <9 µ g/L

<9 µ g/L

Early: 20±26 µ g/L
Delayed: 33±37 µ g/L

Chaparro 2006
Mexico6

Ferritin <9 µ g/L

<9 µ g/L

Early: 35±32 µ g/L
Delayed: 47±38 µ g/L

Gupta 2002
India8

Not reported

Not defined

Early: 80 µ g/L (15-180)
Delayed: 105 µ g/L (30-500)

Geethanath 1997
India11

Not reported

Not defined

Early: 56±4 µ g/L
Delayed: 74±3 µ g/L

 

Is it possible to delay clamping and still collect cord blood?

It is evident that there will be less cord blood to collect if the clamping of the cord has been extensively delayed. Physiological studies in term infants have shown that approximately 70-80% of the blood in the cord and placenta is transferred in the first minute after birth16,30,38,. The study by Andersson et al22 measured the remaining volume in placentas after both early and delayed clamping and found that the volume decreased by 40% when clamping was delayed for 3 minutes and the baby was held 20 cm below the vulva.

Two studies looked specifically at collected cord blood volume as a function of clamping delay. Allan et al 201636 found that a delay of 20-60 sec decreased the collection volume approximately 15%, therby decreasing the fraction of cord blood units with a high enough cell count for public storage (defined as >1.25 billion cells) from 50% to 25% compared with units collected with no delay (<20 sec). In their study, delaying clamping even further to >120 sec, decreased the number of units with high cell counts to 14%. At the International Cord Blood Symposium in June 2016 and in the Dec. 2016 newsletter of Parent’s Guide to Cord Blood, Ciubotariu37 presented data that supported these findings. In this study, early clamping was defined as <60 sec and delayed clmaping >60 sec, and they found that units with high cell content (here defined as >1.6 billion cells) decreased from approximately 18% with early clamping to approximately 2% if the clamping was delayed more than 60 sec.

Would delayed clamping still benefit the baby if the delay is only 30 sec to 1 minute?  Table 2 below shows iron levels as a function of clamping delay time for two studies that provide this data. In both studies, Cernadas et al5 in Argentina and Andersson, et al32 in Sweden, there was no significant difference in blood iron levels between the early versus late clamping groups months after birth, despite variable clamping times, variable months to measurement, and delivery via C-section versus vaginal birth.

 

Table 2:

         Study

Incidence of Iron deficiency and anemia

Ferritin levels; # of infants with  <9 µ g/L

Cernadas, 2010
Argentina5

At 6 months:
15 sec: 6 out of 86 infants
1 min:  3 out of 84 infants
3 min:  2 out of 84 infants

At 6 months:
15 sec: 20 ± 26 µ g/L, 13/86
1 min:  26 ± 26 µ g/L, 10/83
3 min:  33 ± 37 µ g/L, 6/83

Andersson, 2016
Sweden32

At 4 months:
30 sec C-section: 0 out of 52 infants
180 sec, vaginal delivery: 0/148 infants

At 12 months:
30 sec C-section: 1 out of 46 infants
180 sec, vaginal delivery: 0 out of 128 infants

At 4 months:
30 sec C-section: 103 µg/L, 1/55
180 sec, vaginal delivery: 117 µg/L, 0/149

At 12 months:
30 sec C-section: 35 µg/L, 2/46
180 sec, vaginal delivery: 35 µg/L, 2/129

 

Conclusions: Following the recommendations of SOGC26 and ACOG27 , providing the mother is not iron deficient and that the pregnancy is at least 37 weeks gestation, cord clamping at 30 - 60 seconds after birth will ensure a safe outcome for the baby and yet allow for an adequate umbilical cord blood collection if the parents wish to do so. 

Elisabeth Semple PhD is the Director of the Victoria Angel Registry of Hope public cord blood bank and the Scientific Director of the family cord blood bank Cells for Life in Toronto, Canada. She has over 35 years experience in the field of cell collection, processing and banking. After receiving her PhD in Sweden, Dr. Semple has worked with cells in the hospital setting, in academia, and in business, both in Europe and in North America.

References:

  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(11):1241-52.
  2. McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Evidence-Based Child Health. 2014 Jun 16; 9(2):303-397 Cochrane Review Journal DOI:10.1002/ebch.1971.
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  5. Ceriani Cernadas JM, Carroli G, Pellegrini L, Ferreira M, Ricci C, Casas O, Lardizabal J, Morasso Mdel C. The effect of early and delayed umbilical cord clamping on ferritin levels in term infants at six months of life: a randomized, controlled trial. Archivos Argentinos de Pediatria 2010; 108(3):201-208.
  6. 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; 367:1997-2004
  7. Emhamed MO, van Rheenen P, Brabin BJ. The early effects of delayed cord clamping in term infants born to Libyan mothers. Tropical Doctor 2004; 34(4):218-22.
  8. Gupta R, Ramji S. Effect of delayed clamping on iron stored in infants born to anemic mothers. Indian Pediatr 2002; 39:130-5.
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  14. Aziz et al. Early cord clamping and its effects on some hematological determinants of blood viscosity in neonates. published June 1999 on OBGYN.net and verified 2 Dec. 2016
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  16. Linderkamp O, Nelle M, Kraus M, Zilow EP. The effect of early and late cord clamping on blood viscosity and other haemorheological parameters in fullterm neonates. Acta Paediatr. 1992; 81(10):745-50.
  17. Nelle M, Zilow EP, Kraus M, Bastert G, Linderkamp O. The effect of Leboyer delivery on blood viscosity and other haemorheological parameters in term neonates. Am J Obstet Gynecol 1993; 169(1):189-93.
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  21. Al-Tawil MM, Abdel-Aal MR, Kaddah MA. A randomized controlled trial on delayed cord clamping and iron status at 3-5 months in term neonates held at the level of maternal pelvis. J Neonatal-Perinatal Med 2012; 5(4):319-326.
  22. 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.
  23. Philip A. Further observations on placental transfusion. Obstr Gynecl 1973; 42(3):334-43
  24. Spears RL, Anderson GV, Brotman S. The effect of early vs late cord clamping on signs of respiratory distress. Am J Obstr and Gynecol 1966; 95(4):564-568.
  25. Van Rheenen P, de Moor L, Eschbach S, de Grooth H, Brabin B. Delayed cord clamping and hemoglobin levels in infancy: a randomized controlled trial in tern babies. Trop Med International Health 2007; 12:603-15.
  26. SOGC: Leduc D, Senikas V, Lalonde AB, Ballerman C, Biringer A, Delaney M, Duperron L, Girard I, Jones D, Lee LS, Shepherd D, Wilson K; Clinical Practice Obstetrics Committee; Society of Obstetricians and Gynaecologists of Canada. Active management of the third stage of labour: prevention and treatment of postpartum hemorrhage. J Obstet Gynaecol Can. 2009 Oct; 31(10):980-93.
  27. ACOG: The American College of Obstreticians and Gynecologists, Committee opinion. Delayed umbilical cord clamping after birth. Number 684, Jan 2017.
  28. 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 2014; 168:547-54
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  31. Andersson O, Lindquist B, Lindgren M, Stjernquist K, Domellöf M, Hellström-Westas L. Effect of delayed cord clamping on neurodevelopment at 4 years of age. A randomized clinical trial. JAMA Pediatr 2015; 169:631-38.
  32. Andersson O, Hellström-Westas L, Domellöf M. Elective caesarean: does delay in cord clamping for 30 s ensure sufficient iron stores at 4 months of age? A historical cohort study. BMJ Open 2016;6:e012995.
  33. Hooper SB, Binder-Heschl, C, Polglase GR, Gill AW, Kluckow M, Wallace EM, Blank D, te Pas AB The timing of umbilical cord clamping at birth: physiological considerations. Matern Health Neonatol Perinatol. 2016 Jun; 13:2:4.
  34. McAdams R. Time to implement delayed cord clamping. Commentary Obstetrics & Gynecology 2014 Mar; 123(3):549-552
  35. Bayer K. Delayed umbilical cord clamping in the 21st century: indications for practice. Advances in Neonatal Care 2016; 16(1):68-73
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  37. Rodica Ciubotariu, MD PhD. Timing of Umbilical Cord Clamping and Impact on Cord Blood Volume Collected for Banking. Dec. 2016 newsletter Parent;s Guide to Cord Blood Foundation
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