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The Journal of Maternal-Fetal & Neonatal Medicine

ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20

Early versus delayed cord clamping: Effects on hematologic status


in term infants
A. Aktug Ertekin, N. Nihan Ozdemir, Zeki Sahinoglu, Tugba Gursoy, Nazan Erbil & Erdal Kaya
To cite this article: A. Aktug Ertekin, N. Nihan Ozdemir, Zeki Sahinoglu, Tugba Gursoy,
Nazan Erbil & Erdal Kaya (2015): Early versus delayed cord clamping: Effects on hematologic status in term infants, The Journal of
Maternal-Fetal & Neonatal Medicine, DOI: 10.3109/14767058.2015.1105951
To link to this article: http://dx.doi.org/10.3109/14767058.2015.1105951

Accepted author version posted online: 13 Oct 2015.

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Taylor &.
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Taylor & Francis Group

THE JOURNAL OF

MATERNALFETAL
& NEONATAL
MEDICINE
EdHorc-nvChmf

Gian Carlo Di Renzo Dev


Maulik

Covered in
Index
Medici and
MEDUNE

Just Accepted by The Journal of Maternal-Fetal & Neonatal Medicine


Early versus delayed cord clamping: Effects on hematologic status in
term infants
A. Aktug Ertekin, N. Nihan Ozdemir, Zeki Sahinoglu, Tugba Gursoy, Nazan
Erbil, Erdal Kaya
doi: 10.3109/14767058.2015.1105951
Abstract
Objective: We investigated the effects of delayed and early clamping of the
cord on the hematologic status of the baby at birth and at the end of
second month.
Methods: Umbilical cord of 74 babies were clamped in the first 30 seconds
(Group 1) and 76 were clamped at 90-120 seconds (Group 2). Levels of
hemoglobin, hematocrit, iron and ferritin were analysed from the umbilical
cord blood at birth and from the venous samples at the end of second
month.

Results: Hemoglobin, hematocrit, iron and ferritin levels of cord blood


were similar in both groups. However, their levels other than ferritin were higher in Group 2 at the end of
second month. Two babies had respiratory distress and twelve neonates received phototherapy in Group 2
whereas only five neonates received phototherapy in Group 1.
Conclusion: Term babies to whom delayed cord clamping was performed had improved hematological
parameters at the end of second month. Therefore, delaying cord clamping in these babies may be a favorible
approach in preventing anemia.

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Early versus delayed cord clamping: Effects on hematologic


status in term infants
A.Aktug Ertekin 1, Corresponding author, Department of Health
Sciences, Uskudar University, Istanbul, Turkey
GSM : +90 532

2877561 Fax :
+90

3594112
mail:

216
E-

aaertekin@gmail
.com

N.Nihan Ozdemir 2, Department of Obstetrics, Zeynep


Kamil Women and Childrens Disease, Training and
Research Hospital, Istanbul, Turkey
GSM : +90 538 6381551 E-mail :
nihanaslaner@gmail.com

Zeki Sahinoglu 2, Department of Perinatology, Clinic of

Obsterics and Gynecology, Anadolu Health Center, Kocaeli,


Turkey
GSM : +90 532 6114546
E-mail : zeki.sahinoglu@anadolusaglik.org
Tugba Gursoy 3, Department of Pediatrics, Koc University
School of Medicine, Istanbul, Turkey

GSM : +90 533 5445944 E-mail : tgursoy@ku.edu.tr


Nazan Erbil 4, Department of Pediatrics, Zeynep Kamil
Women and Childrens Disease, Training and Research
Hospital, Istanbul, Turkey GSM : +90 532 5230815 Email : erbilnazan@hotmail.com

Downloaded by [New York University] at 12:07 13 November 2015

Erdal Kaya 5, Department of Obstetrics and Gynecology,

Bagcilar Training and Research Hospital, Istanbul, Turkey

GSM : +90 536 9799494


E-mail : erdalkaya06@hotmail.com
1 Department of Health Sciences, Uskudar University, Istanbul,
Turkey
2 Department of Obstetrics, Zeynep Kamil Women and Childrens

Disease, Training and Research Hospital, Istanbul, Turkey


3 Department of Pediatrics, Women and Koc University, School
of
Medicine,
Istanbul, Childr
Turkey
4 Department of Pediatrics,
and Childrens Disease,

Hospital, Istanbul, Turkey

5 Department of Obstetrics and


Training and Research Hospital,
Istanbul, Turkey
Short title: Term babies
clamping has improved

parameters and this is a


approach in preventing
Keywords:

hemoglobin,
Abstract:

early

and

hematocrit,

Q
*

Zeynep Kamil Women


Training and Research

Gynecology,

Bagcilar

with delayed cord


hematological
favorible
anemia

delayed cord clamping,


iron, ferritin

Objective: We investigated the effects of delayed and early


clamping of the cord on the hematologic status of the baby
at birth and at the end of second month.

Methods: Umbilical cord of 74 babies were clamped in the


first 30 seconds (Group 1) and 76 were clamped at 90-120

seconds (Group 2). Levels of hemoglobin, hematocrit, iron


and ferritin were analysed from the umbilical cord blood at

birth and from the venous samples at the end of second


month.

Results: Hemoglobin, hematocrit, iron and ferritin levels of


cord blood were similar in both groups. However, their
levels other than ferritin were higher in Group 2 at the end
of second month. Two babies had respiratory distress and

twelve neonates received phototherapy in Group 2 whereas


only five neonates received phototherapy in Group 1.

Conclusion: Term babies to whom delayed cord clamping

was performed had improved hematological parameters at

the end of second month. Therefore, delaying cord

clamping in these babies may be a favorible approach in


preventing anemia.

Keywords: early and delayed cord clamping, hemoglobin,


hematocrit, iron, ferritin.
Presented in oral format at the 20

th

National Neonatalogy

Congress, April 15-18, 2012, Bodrum, Turkey.

Anemia is an important health problem all over the world,

especially in developing or low income countries among

newborn infants or children and it is also associated with


poor neurodevelopment of the infant. Iron in the blood is
essential for brain development, neurotransmitter function,

glial and neuronal energy metabolism and myelination [15]. In young children, iron deficiency anemia is associated

with behavioral and cognitive deficits, impaired motor


development

and

altered

affective

responding

[6,7].

Preventing infants and children from anemia is an


important health policy of the countries and for overcoming
this problem there is no exact consensus about early and
delayed cord clamping of the neonate or active and passive

management of the third stage of labor for preventing

postpartum anemia in women. Both managements have


advantages and disadvantages. For the mother, early cord

clamping can prevent her from anemia and shortens the

third stage of labor but there is no known favorable effect


for

the

neonate

[8].

The

main

purpose

of

active

management in the third stage of labor by administering


uterotonic drugs, early cord clamping (less then thirty

seconds or as soon as possible) and gentle traction of the


cord is to prevent postpartum hemorrhage, which may

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increase maternal morbidity and mortality. Another logic of

the use of uterotonic drugs is to allow more blood

transfusion from placenta to the baby with the contractions


of the uterus [9]. In delayed cord clamping, approximately

80-100 ml of blood can be transferred to the baby which

contributes 20-30 mg/kg of iron [10,11]. In preterm


neonates, delayed cord clamping has also secondary
favorable outcomes such as reduction in the incidence of

transfusion, respiratory support, intraventricular hemorrhage


and sepsis [12,13]. There may be some adverse effects

with delayed cord clamping, which are hyperbilirubinemia,


increased

need

for

respiratory symptoms
[14-17].

phototherapy,

polycythemia

and

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Methods
This prospective case-control study was conducted in
Zeynep Kamil Maternity and Childrens Disease, Training

and Research Hospital, between August 1, 2011 and


November 30, 2011. The study was approved by the local

Ethics Committee. The inclusing criteria were as follows;

neonates born to single and term pregnancies (37 to 41 +6


weeks), non-smoking and healthy mothers. The exclusion
criteria were; preterm and multiple pregnancies, operative
deliveries, neonates necessitating recussitation, presence of

fetal anomalies, intrauterine growth restriction, maternal


diseases or drug use, placental anomalies and request for
cord blood banking.

The primary outcome was to investigate the effect of early

and delayed clamping of the umbilical cord on the


hematologic status of the neonate at birth and at the end of
second month. The secondary outcomes were to analyse

effect of delayed clamping on the incidence of maternal

blood loss, neonatal respiratory distress, hyperbilirubinemia,


phototherapy need, neonatal intensive care unit (NICU)
admission and length of hospitalisation.

Informed consent was obtained from the mothers who met


the inclusion criteria and willing to participate in the study.

Mother and infant pairs were divided in 2 groups, early


(Group 1) and delayed (Group 2) cord clamping. In Group

1 cord was clamped in the first 30 seconds and in Group 2


cord was clamped 90 to 120 seconds after delivery.

Delivery of the infant shoulder was accepted as the zero


time and a staff in all births recorded the clamping time
with a stop-watch. In cesarean and vaginal births, babies

were put on a newborn table in which the level of the baby

and uterus was similiar in both groups and then the cord
was clamped early or delayed. After clamping the umbilical
cord, venous blood was obtained from the double clamped
umbilical cord of both groups for hemoglobin, hematocrit,
iron and

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ferritin analyses and no blood was withdrawn from the


peripheral vein because of the study design (major

comment 2). Cord blood was collected in EDTA tubes


(BD Vacutainer, USA) for hemoglobin, hematocrit and in

serum separator tubes (BD Vacutainer tube, SST, USA) for

iron and ferritin. Blood samples were transported to the


hospital clinical chemistry laboratory where they were

analysed within 15 minutes after obtaining the samples. In


our clinic, during the third period of delivery, we did not
use any uterotonic drugs before the expulsion of placenta

(minor comment 1). All newborns were examined by a


pediatrician in the first 24 hours and early breastfeeding

was encouraged. As a general rule mothers giving birth via


vaginal deliveries were discharged after 24 to 72 hours and

mothers giving birth via cesarean section were discharged


24 to 96 hours after puerperal education and drug

prescription. At the end of second month, the same

hematologic parameters were analysed from the venous


blood with the same method in both groups.

Statistical Package for the Social Sciences for Windows,

16.0 version was used for the statistical analyses. Students


t test and X were used for comparison of two groups and

for statistical significance, type I error was calculated as


5%.

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Results
The demographic characteristics of the mother-infant pairs
and hematological parameters of the mothers did not differ

between the groups (Table 1). However, delivery by

cesareanne section was significantly higher in Group 1. In


Group 1 and Group 2 average cord clamping times were
20,5 and 101,1 seconds, respectively (major comment 1).
Hematological parameters of the cord blood and at the age

of 2 months of the infants in both groups are given in


Table 2. Though cord blood hemoglobin hematocrit and
iron levels did not differ between the groups, they were

significantly higher in infants whose cord were clamped


late at the age of 2 months (Table 2). However, ferritin

levels of both groups did not differ neither in cord blood


samples nor in blood samples obtained at two months of
age.

Table I
Table II
Five infants (6,8%) in Group 1 and 12 (15,7%) infants
in Group 2 needed phototherapy (p=0.08). Mean of

maximum bilirubin level observed was 17.6 1.8 g/dL


in Group 1 and 17.9 2.1 g/dL in Group 2 (p=0.7)
(major comment 3). Only the neonates who received

phototherapy were subjected to blood withdrawal of about

2 ml for direct and indirect bilirubin, blood type and

direct coombs test (major comment 5). Two of the babies


in Group 2 had mild tachypnea that lasted less than two
hours, however, there was no NICU admission in both
groups. None of the infants had polycythemia. No

postpartum hemorrhage was observed in either group. No


babies received iron therapy. All the babies were

exclusively breastfed and received 400 IU vitamin D

starting from the first week of life up (major comment 4).


No baby had an infectious event during follow up (major
comment 6).

Discus
sion
World
Health Organisation advises late cord clamping;
however there is a debate on the optimal time for cord
clamping [18]. If the cord clamping is deferred more than

60 seconds, blood flow between the baby and placenta

continues and is usually completed by 120 seconds and


named as placental transfusion. This allows the transfusion
of 80-100 ml of blood which constitutes about one third or

a quarter of the newborns total blood volume [10]. Even


though not fully clear, placental transfusion could be
considered as a cause of some undesirable effects in the

newborn and as well as in the mother such as polycytemia,

jaundice, respiratory symptoms, phototherapy need and


postpartum uterine hemorrhage. In this study, although the

incidence of jaundice necessitating phototherapy was higher


in infants whose cords were clamped late, this difference

did not reach statistical significance (6,8% vs 15,7%;

p=0,08) as confirmed in the literature [19-22]. As


mentioned in the material- methods, we paid attention to

put all the neonates on a newborn table which was


approximately at the same level with the uterus to facilitate

blood transmission from the placenta to the newborn.


However, in a multicenter trial at three university-affiliated

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Discus
sion
hospitals
in Argentina, the autors mentioned that position of
the newborn baby before cord clamping does not seem to

affect volume of placental transfusion. Therefore, mothers


could safely be allowed to hold their baby on their

abdomen or chest. This change in practice might increase


obstetric compliance with the procedure, enhance maternalinfant bonding and decrease iron deficiency in infancy [23].

We found that delaying cord clamping up to 90 to 120


seconds increases hemoglobin, hematocrit and iron levels

significantly at the second month. Although there was no


difference of iron levels between early and delayed cord

clamping groups at birth, a significantly higher iron level


was achieved at the second month of age in the delayed

clamped group. An increase of serum iron level rather than


hemoglobin, allows more tissue

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oxygenation, proper myelinization, improved hematologic

parameters and less ventilator support [24,25]. Iron is an


essential trophic factor that is required for oxygen

consumption and ATP production. The brain has a

relatively high rate of oxygen consumption compared to


other organs. Oligodendrocytes are the principal cells in the

central nervous system that stain for iron under normal


conditions. The timing of iron delivery to oligodendrocytes
during myelinization is essential because hypomyelination
and the associated neurological sequelae persist long after
the systemic iron deficiency has been corrected. Due to the

hypomyelination, most common neurological signs of iron


deficiency in children include poor school performance,

decreased cognitive abilities and behavior problems [26].


Furthermore, these neurological sequelae persist even after
iron supplementation.

While prominent positive effects of delayed cord clamping


on hemoglobin, hematocrit and serum iron levels were well
established, clamping cord after the first breath of the
neonate was shown to have improving effect on neonatal

cardiac and pulmonary functions [9]. In a study including

of 15.563 newborns outcomes in a rural hospital, the risk


of death/NICU admission was consistently higher if cord

clamping occurred before spontaneous respiration [27].

While infants of birth weight <2500 g were more likely to


die or be admitted at NICU, the risk of death or NICU
admission decreased by 20% for every 10-second delay in

cord clamping after spontaneous respiration. The authors

concluded that healthy self-breathing neonates were more


likely to die or be admitted if cord clamping occured
before

or

respiration.

experimental

demonstrating

immediately

These

after

clinical

findings

smoother

of

onset

of

observations

an

animal

cardiovascular

spontaneous

support

based

transition

the

study

delayed cord clamping after initiation of ventilation [9].

with

It was known that umbilical cord blood contains various

valuable stem cells such as haematopoietic stem cells,


endothelial cell precursors, mesenchymal progenitors and
multipotent/pluripotent

lineage

preventing anemia in newborns by

stem

cells.

Besides

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delayed cord clamping, the merit of delayed cord clamping

has been magnified by realizing first stem cell transfer. In


view of this purpose, not only in preterm births, delayed

cord clamping should be encouraged in term births too


[28].

We conclude that delayed cord clamping in term babies


had no effect on hematologic status at birth but had

improving effects on hemoglobin, hematocrit and iron levels


at the second month without any serious complication.
However, phototherapy need may be increased in delayed
group.

Delayed cord clamping could be considered an appropriate

and easy to perform approach in increasing iron levels,


circulating blood volume and stem cells which seem to be

key factors in myelinization and smooth passage to


extrauterine circulation in term neonates. Long term follow
up studies should be performed to evaluate the effects of

higher iron levels on the neurocognitive outcome of the


babies.

Acknowledgements
The authors report no acknowledgements.
Declaration of interest
The authors report no declarations of interest

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Tables
Table I. The demographic characteristics and hematological
parameters in both groups.
Group 1 n: Group 2 n:76
74
26,55,2
2 (1-3)

Age (mean SD)


Gravida
Cord clamping
20,5+6
time
(seconds, mean
SD)
Maternal Hb, g/dl 13,111,7
(mean SD)

Maternal Hct, %
34,73
(mean
SD)
Maximum
17.6 1.8
bilirubin
level (g/dL, mean

SD)
Delivery route,
71 (95,9)
vaginal
birth, n (%)
Birth weight (g)
3357329
Gestational age
38,9 0,9
(weeks)
5th minute Apgar
9 (9-9)
score

26,95,4
2 (1-3)

0,66
0,1

101,1+8,3

<0,001

11,61,4

0,48

34,64

0,86

17.9 2.1

0.7

53 (69,7)

<0,001

3268383

0,13

/V

39,1 1,1
9 (9-9)

0,23
0,58

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Table II. Hematological parameters of cord blood and at the


age of 2 months of the infants in both groups.
Cord blood levels

Second month blood

Group 1 Group 2 p
Hb,
g/dl,
(mean
SD)
Hct,
%,
(mean

15,41 15,21,8 0,5


,5
3

9,90,9

10,30,
8

0,0
03

45,74 46,16
,6

292,2

30,32,
5

0,00
1

0,0 68,525,3 79,625


53
,5

0,00
8

SD)
Fe,
161,2 14650
mcg/dl, 45,9
(mean
SD)
Ferriti
n,

0,6
2

2222 171,91 0,0


00
14,8
58
levels
ng/ml (mean SD)
p< 0.05: statistically significant

240,314 231,11
7,7
23

0,
68

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