the early effects of delayed cord clamping in term
infants born to libyan mothers
Musbah Omar Emhamed1, Patrick van Rheenen2, Bernard J Brabin1,2
1 Child and Reproductive Health Group, Liverpool School of Tropical Medicine,
2 Emma Kinderziekenhuis, Academic Medical Centre Amsterdam, Nether-
Tropical Doctor 2004; 34: 218-222
This study was conducted to evaluate thehaematological effects of the timing of
umbilical cord clamping in term infants 24 h after birth in Libya. Mother-infant
pairs were randomly assigned to early cord clamping (within10 s after delivery)
or delayed clamping (after the cord stopped pulsating). Maternal haematological
status was assessed on admission in the delivery room. Infant haematological
status was evaluated in cord blood and 24 h after birth. Bilirubin concentration
was assessed at 24 h. 104 mother-infant pairs were randomized to delayed (n=58)
or early cord clamping (n=46). At baseline the groups had similar demographic
and biomedical characteristics, except for a difference in maternal haemoglobin,
which was significantly higher in the early clamping group (11.7 g/dL (SD 1.3)
versus 10.9 g/dL, (SD 1.6); P=0.0035). Twenty-four hours after delivery the mean
infant haemoglobin level was significantly higher in the delayed clamping group
(18.5 g/dL versus 17.1g/dL; P=0.0005). No significant differences were found in
clinical jaundice or plethora. Surprisingly, blood analysis showed that two babies
in the early clamping group had total serumbilirubin levels (>15mg/dL) that ne-
cessitated phototherapy. There were no babies in the late clamping group who
required phototherapy. Three infants in the delayed clamping group had polycy-
thaemia without symptoms, for which no partial exchange transfusion was neces-
sary. Delaying cord clamping until the pulsations stop increases the red cell mass
in term infants. It is a safe, simple and low cost delivery procedure that should be
incorporated in integrated programmes aimed at reducing iron deficiency anae-
mia in infants in developing countries.
Iron deficiency anaemia (IDA) is the most common nutritional disorder world-
wide. Its prevalence is highest among children aged under five years in devel-
oping countries, where approximately 50% are affected.1 Severe anaemia in
infancy is a life threatening condition and a major contributor to infant mortal-
ity in developing countries.2-4 IDA has been associated with impaired cognitive
development in children under five. These children fail to catch up with iron
Strategies to reduce IDA in infants include iron supplementation and iron-
fortification. Although these measures have been shown to be clinically effec-
tive,7-9 they are either cost-ineffective or difficult to implement, especially in
A first step towards reducing anaemia in infancy can be taken during birth.
Delayed cord clamping or placental transfusion could be a cost-effective inter-
vention to improve the iron status of infants by enhancing their red cell mass.
The main objective of this study was to examine the effect of the time of um-
bilical cord clamping in term infants on haematological status 24 hours after
birth. A second objective was to assess possible adverse effects, especially hy-
perviscosity and hyperbilirubinaemia. There have been controlled trials evalu-
ating the short-term haematological effects of delayed cord clamping in term
infants,10-14 but as far as we know this is the first randomised controlled trial.
subjects and methods
Term infants delivered at Tripoli Medical Centre (TMC) in Libya between April
and June 2003 were enrolled. Their mothers were contacted while in their first
stage of labour to obtain informed consent. After giving consent, and prior to
vaginal delivery, the infants were randomly assigned by means of sealed opaque
envelopes to either delayed cord clamping (DCC) or immediate cord clamping
(ICC). In the DCC group the umbilical cord was clamped after it stopped pulsat-
ing. The exact time was recorded by use of a stopwatch, with complete expulsion
of the infant as the starting point. In the ICC group clamping was done within
10 seconds after delivery, which was the standard delivery practice at that time
in TMC. Following vaginal birth the infant was placed on the mothers abdo-
men and dried and wrapped in a warm towel. Oxytocin was given to the mother
intramuscularly after cord clamping. Common practice is to give oxytocics with
the delivery of the anterior shoulder. This delivery practice was adapted for the
trial period to minimise confounders, as the administration of oxytocin in the
third stage might speed up placental transfusion.15 The nurse midwives attend-
ing the deliveries were closely monitored by one of the authors (MOE).
All subjects meeting the following selection criteria were included: expected
birth weight ≥ 2500 g, gestational age between 37 and 42 weeks (estimated by
early ultrasound) and singleton birth. Mother-infant pairs were excluded when
the baby had low birth weight (< 2500 g) or when the gestational age (as as-
sessed by Ballard-external method) was less than 37 weeks. Other exclusion
criteria were maternal gestational diabetes or (pre)eclampsia, instrumental
delivery, serious haemorrhage during pregnancy or delivery, major congenital
abnormalities (neural tube defects, respiratory distress syndrome) and the need
for early cord clamping (medical history of post-partum haemorrhage; tight
nuchal cord; resuscitation).
One venous blood sample was taken from the mother upon arrival in the la-
bour ward for estimation of maternal haemoglobin (Hb) and haematocrit (Ht).
Women with Hb < 10 g/dL were considered to be anaemic. Before delivery a
small structured survey questionnaire was used to gather socio-economic and
demographic details from the mothers, as well as information on reproduc-
tive health. A sample of cord blood was collected from the placental side after
clamping and ligating the fetal side for Hb and Ht estimation. Babies with
cord Hb < 12.5 g/dL were considered to have fetal anaemia. Before discharge
home (16-24 hours after birth) the babies were assessed for clinical signs of
polycythaemia, hyperviscosity or hyperbilirubinaemia, and, if necessary, an es-
timation of the gestational age was done by using the Ballard-external method.
Finally, an infant venous blood sample was taken for Ht and bilirubin analysis.
Polycythaemia was defined as venous Ht > 65%. Phototherapy was considered
to be necessary when bilirubin levels exceeded 15 mg/dL on day 1.
Based on the results of a recent systematic review,16 we expected a difference
in mean haemoglobin between the ICC and DCC group at 24 hours of 1.5 g/dL
with a standard deviation of 2.0 g/dL. On this assumption with a power of 90 %
and a confidence level of 95%, a sample size of 40 babies was required in each
As the aim of this study was to evaluate the effects of late cord clamping
under ideal circumstances, data were analysed according to the per-protocol
principle. Epi Info 2002 (Centers for Disease Control and Prevention, CDC,
USA) was used for data analysis. The t-test for independent samples was used
to compare group means for normally distributed data. When variances were
not homogeneous the Mann-Whitney rank-sum test was used. A P-value < 0.05
was considered significant.
Ethical approval for the study was given by the Ethics Committee of the Liver-
pool School of Tropical Medicine and by local authorities of the departments of
Obstetrics & Gynaecology and Paediatrics in TMC.
There were 112 mother-infant pairs eligible for inclusion (figure 1); 62 were
randomised to DCC and 50 to ICC. Eight mother-infant pairs, equally distrib-
uted over both randomisation groups, were excluded from the final analysis.
The infants needed resuscitation for intrapartum asphyxia. As a consequence,
58 mother-infant pairs remained in the DCC group (mean clamping time: 215
seconds (SD 51), and 46 in the immediate clamping group (mean 13 seconds
(SD 6)). The mothers in the ICC and DCC groups were comparable in terms
of age, parity, gestational age, ultrasound confirmation, level of education and
antenatal iron supplementation. The mean maternal (Hb) level on admission
to the labour ward was higher in the ICC group (11.7 g/dL (SD 1.3)) than in the
DCC group (10.9 g/dL (SD 1.6), and this difference was significant (p = 0.0035).
The proportion of women with anaemia at delivery was also higher in the DCC
group: 29% versus 9% (p=0.0096). Other maternal baseline characteristics were
not significantly different (Table1).
Figure. 1 Recruitment into the study. DCC=delayed cord clamping; ICC=immediate cord clamping Articles
112 mother-infant pairs
eligible for inclusion
62 pairs DCC
50 pairs ICC
46 pairs ICC
45 pairs ICC
58 pairs DCC
57 pairs DCC
1 pair left
1 pair left
Table 1. Maternal baseline characteristics
Variable Early clamping
Maternal age in yrs 28.9 (4.8) 28.4 (4.7)0.64
Parity (mean ± SD)
Iron supplementation in pregnancy (%)78 810.73
Number of antenatal visits to clinic 6.8 (3.2)6.2 (3.2) 0.36
Ultrasound in first trimester (%)91 930.74
Oxytocics prior to clamping (%)
Hb on admission to labour ward (g/dL)
Proportion maternal anaemia (%)
(Hb < 10 g/dL)
0.0035 11.7 (1.3)10.9 (1.6)
Infant baseline characteristics did not differ significantly (Table 2). Low birth
weight was not observed in any infant. Cord Hb and Ht levels were comparable
in both groups. The prevalence of fetal anaemia was higher in the DCC group,
although this difference was not significant. Polycythaemia was not observed at
birth. There was no correlation between maternal and cord haemoglobin in either
the ICC or DCC group.
Table 2 Infant baseline characteristics
Variable Early clamping
Clamping time (sec)12.8 (5.5) 214.6 (50.6) 0.0000
Gestational age (weeks) 40.0 (1.4)39.8 (1.4) 0.36
Birthweight (grams) 3428 (424)3390 (421)0.65
Female sex (%)46 550.33
Cord haemoglobin (g/dL)
Proportion Fetal Anaemia (%)
(Hb < 12.5 g/dL)
15.4 (1.4) 14.9 (1.7)0.12
45.0 (4.6)44.1 (5.8)0.37
Data are mean (SD) unless stated otherwise
Data are mean (SD) unless stated otherwise
A single child was lost to follow-up in each group, as their parents had taken them
home before they could be reviewed. Evaluation after 24 hours revealed no sig-
nificant differences in clinical jaundice or the proportion of infants with clinical
plethora. There were no significant differences in serum total bilirubin levels at
24 hours, although surprisingly 4.6% of the infants in the ICC group had biliru-
bin levels (>15 mg/dL) that necessitated phototherapy.
The Ht level was significantly higher in the DCC group (p = 0.0037), but only
5% of infants in this group had polycythaemia. Hb levels after 24 hours showed
higher values in the DCC group (18.5 g/dL (SD 2.1) versus 17.1 g/dL (SD 1.9))
and these differences were significant (p = 0.0005). The infants haematological
outcomes are summarised in Table 3.
Table 3. Infant haematological outcome after 24 hours
Serum bilirubin (mg/dL)6.1 (3.0)5.8 (1.3)0.38
Proportion (%) above phototherapy threshold
(bilirubin > 15 mg/dL)
Clinical plethora (%) 24.440.40.09
Haemoglobin (g/dL)17.1 (1.9)18.5 (2.1)0.0005
Difference in cord haemoglobin and at 24 hrs
1.7 (1.7) 3.5 (1.9)0.0000
Haematocrit (%)49.3 (5.7) 52.9 (6.3)0.0037
Difference in cord haematocrit and at 24 hrs
4.4 (5.6)8.7 (5.7)0.0002
Proportion polycythaemia (%) (Hct > 65%) 0 5.3 0.12
Data are mean (SD) unless stated otherwise
The aim of this study was to evaluate whether DCC could enhance red cell mass
in term infants in Libya. We found a difference in the mean Hb and Hct levels
of infants at 24 hours after delivery in favour of the DCC group. This difference
is statistically significant and is possibly of clinical importance. This result is in
accordance with earlier published studies on the short-term effects of placental
transfusion.16 It should be noted that the incidence of moderate maternal anaemia
(Hb < 10 g/dL) was significantly higher in the group randomised for DCC, while
both groups were comparable for all other variables. No women had severe anae-
mia (Hb<7g/dL). The fact that a considerable number of babies (6 out of 104) were
found to have fetal anaemia, can possibly be explained by the existence of α-thal-
assaemia in the study population, which is known to reduce cord Hb levels.
Maternal iron deficiency has also been related to fetal anaemia in a study from
Malawi.17 Four randomised controlled trials have been published that examined
longer-term effects of DCC in developing countries have been published. Two
found a significant difference in Hb levels at 2-3 months in favour of the DCC
group.18;19 The other two studies showed no difference in indicators for infant
iron status.20;21 Three controlled trials from Germany (published in four papers)
showed a significant increase in Ht levels in favour of DCC.10-13 This difference
was seen by 2-4 hours after delivery, and remained significant during the follow-
ing five days.
Hyperbilirubinaemia, polycythaemia and hyperviscosity syndrome are frequent-
ly mentioned adverse effects of placental transfusion. In our study in term infants
no significant difference was found between the DCC and ICC groups in total se-
rum bilirubin levels at 24 hours, the number of infants requiring phototherapy, or
the prevalence of plethoric skin and polycythaemia. None of the children showed
signs of hyperviscosity syndrome (cyanosis, feeding difficulties, tachypnea or neu-
rological depression). Blood glucose levels were not checked routinely, but none of
the children showed signs of hypoglycaemia. Placental transfusion in term infants
was not associated with perinatal complications in this study.
No previously published trials reported any clinical manifestations of poly-
cythaemia.10-13;18-21 The German trials reported that some newborns with DCC
had bilirubin levels > 15 mg/dL. It was not stated how many days after delivery
these neonates were assessed. Neither did they report whether phototherapy or
exchange transfusions were needed. A trial from Canada examined both pre-term
and term infants.14 When analysing the data for term infants separately no cases
of hyperbilirubinaemia were found.
The major objective of this trial was to evaluate whether DCC could improve the
haematological status of infants. The difference we found in the mean Hb and Ht
levels of infants at 24 hours after delivery in favour of the DCC group is possibly
of clinical importance. It is estimated that in full-term infants placental transfu-
sion can increase red cell mass by 25-33%.22;23 Iron stores in the term newborn are
normally adequate to maintain iron sufficiency for approximately four months
of postnatal growth.24 Improved iron status from these additional red cells might
increase the stores sufficiently to cover the first 5-6 months.
A recent systematic review showed that DCC in premature babies should be done
with more caution. Delaying cord clamping in premature babies for more than
1 minute increases the risk of complications such as polycythaemia and hyper-
bilirubinaemia. It seems advisable to delay clamping of the umbilical cord in this
group of neonates for not more than 45-60 seconds.25
The policy of delayed cord clamping is in contrast with active management of
the third stage of labour to reduce post-partum haemorrhage. Active manage-
ment involves ICC, prophylactic use of oxytocic drugs before delivery of the
placenta and controlled cord traction.26 In our opinion delaying cord clamping
can be done safely in selected groups. Women who have a history of post-partum
haemorrhage should be exempted from this delivery procedure. Although the
administration of oxytocin was postponed until after cord clamping in this study,
this is not necessary in practice. Early intramuscular injection of oxytocin can
even speed up placental transfusion.15
Delaying cord clamping until the pulsations stop is a physiological way of treat-
ing the cord and is not associated with adverse effects, at least in term vaginal
deliveries. Many children living in less developed countries belong to anaemia
risk groups (low birthweight; severe maternal anaemia, chronic infection, iron
deficient diets after 5-6 months) and should therefore be given the opportunity to
boost their iron stores at birth. DCC, which is a safe, simple and low-cost delivery
procedure, should be incorporated in the routine labour management. It could
serve as an additional cost-effective intervention within integrated programmes
aimed at reducing IDA in infants in developing countries.
We thank all doctors and nurse midwives of Tripoli Medical Centre who have
contributed to this study with their warm dedication and cooperation.
1. DeMaeyer E, Adiels-Tegman M. The prevalence of anaemia in the world.
World Health Stat Q 1985; 38: 302-16.
2. Brabin BJ, Premji Z, Verhoeff F. An analysis of anemia and child mortality. J
Nutr 2001; 131: 636S-45S.
3. Commey JO,.Dekyem P. Childhood deaths from anaemia in Accra, Ghana.
West Afr J Med 1995; 14: 101-4.
4. Slutsker L, Taylor TE, Wirima JJ, Steketee RW. In-hospital morbidity and mor-
tality due to malaria-associated severe anaemia in two areas of Malawi with
different patterns of malaria infection. Trans R Soc Trop Med Hyg 1994; 88:
5. Grantham-McGregor S, Ani C. A review of studies on the effect of iron defi-
ciency on cognitive development in children. J Nutr 2001; 131: 649S-66S.
6. Stoltzfus RJ, Kvalsvig JD, Chwaya HM, Montresor A, Albonico M, Tielsch JM
et al. Effects of iron supplementation and anthelmintic treatment on motor
and language development of preschool children in Zanzibar: double blind,
placebo controlled study. BMJ 2001; 323: 1389-93.
7. Alonzo GM, Menendez C, Font F, Kahigwa E, Kimario J, Mshinda H et al.
Cost-effectiveness of iron supplementation and malaria chemoprophylaxis in
the prevention of anaemia and malaria among Tanzanian infants. Bull World
Health Organ 2000; 78: 97-107.
8. Brabin BJ. Iron supplementation to control anaemia. In Nestel P, ed. Iron
interventions for child survival. London: OMNI proceedings, 1995: 67-71.
9. Ekvall H, Premji Z, Bjorkman A. Micronutrient and iron supplementation
and effective antimalarial treatment synergistically improve childhood anae-
mia. Trop Med Int Health 2000; 5: 696-705.
10. Linderkamp O, Nelle M, Kraus M, Zilow EP. The effect of early and late cord-
clamping on blood viscosity and other hemorheological parameters in full-
term neonates. Acta Paediatr 1992; 81: 745-50.
11. Nelle M, Zilow EP, Kraus M, Bastert G, Linderkamp O. The effect of Leboyer
delivery on blood viscosity and other hemorheologic parameters in term neo-
nates. Am J Obstet Gynecol 1993; 169: 189-93.
12. Nelle M, Zilow EP, Bastert G, Linderkamp O. Effect of Leboyer childbirth on
cardiac output, cerebral and gastrointestinal blood flow velocities in full-term
neonates. Am J Perinatol 1995; 12: 212-6.
13. Nelle M, Kraus M, Bastert G, Linderkamp O. Effects of Leboyer childbirth on
left- and right systolic time intervals in healthy term neonates. J Perinat Med
1996; 24: 513-20.
14. Saigal S, ONeill A, Surainder Y, Chua LB, Usher R. Placental transfusion and
hyperbilirubinemia in the premature. Pediatrics 1972; 4: 406-19.
15. Yao AC, Lind J. Blood flow in the umbilical vessels during the third stage of
labor. Biol Neonate 1974; 25: 186-93.
16. van Rheenen P,.Brabin BJ. Late umbilical cord clamping as an intervention
for reducing iron deficiency anaemia in term infants in developing and indus-
trialised countries: a systematic review. Ann Trop Paediatr 2004; 24: 3-16.
17. Brabin BJ, Kalanda BF, Verhoeff FH, Chimsuku L, and Broadhead RL. Risk
factors for fetal anaemia in a malarious area of Malawi. Ann Trop Paediatr
2004; 24; 311-321.
18. 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.
19. 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;
20. 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:
21. Lanzkowsky P. Effects of early and late clamping of umbilical cord on infants
haemoglobin level. BMJ 1960; 2: 1777-82.
22. Linderkamp O. Placental transfusion: determinants and effects. Clin Perinatol
1982; 9: 559-92.
23. Yao AC, Moinian M, Lind J. Distribution of blood between infant and placenta
after birth. Lancet 1969; 2: 871-3.
24. Oski FA. Iron deficiency in infancy and childhood. N Engl J Med 1993; 329:
25. van Rheenen, P and Brabin, B. J. Late umbilical cord clamping as an inter-
vention for reducing anaemia in low birthweight infants: a systematic review.
26. Prendiville WJ, Elbourne D, McDonald S. Active versus expectant manage-
ment in the third stage of labour (Cochrane Review). In: The Cochrane Library,
issue 4, Chichester, UK: John Wiley & Sons, Ltd, 2003.
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