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A Randomized Controlled Trial

Andre Inigo MD, (Principal Investigator)

Department of Pediatrics, San Juan De Dios Hospital


Cord clamping in relation to delivery of the newborn is still flocked with many

controversial issues. The usual practice is to clamp the cord after 10-15 seconds from

birth. However, there has been no sound evidence in favor of this approach

in comparison to the millennial practice of clamping the cord between 1 and 3 minutes

after birth.1-2 Three studies observed that delayed cord clamping could contribute to

preventing iron-deficiency anemia in the first year of life. 3-5

A recent systematic

review confirms the benefit of delayed cord clamping. 6 The reason for this effect is

based on the fact that after birth the newborn is delivered with a placental transfusion

of 80 mL of blood at 1 minute after birth and 100 mL at 3 minutes after birth. 7

Compared with early clamping, a delay of around 2–3 min provides an additional

40 mL of blood per kg of bodyweight.8-9 For a 3·2 kg infant with a haemoglobin

concentration of 170 g/L at birth, this additional blood amounts to an additional 75 mg

of iron added to iron stores, sufficient to meet the needs of a 6–11 month-old infant for

more than 3 months.10

This study re-examines more delayed clamping of about 3 minutes on the

venous hematocrit of term infants born in this institution.


What is the effect of delayed cord clamping on the venous hematocrit of term,

healthy neonates in a randomized controlled trial ?


To compare the effect of delayed versus early cord clamping on the venous

hematocrit of term, healthy neonates.


1. To determine the clinical profile of term neonates among those with early versus

delayed cord clamping in terms of:

a. Sex
b. Gestational age
c. Birth weight, birth length
d. APGAR scores at 1 and 5 minutes
e. Ballard’s Maturity Rating
2. To determine the maternal clinical characteristics neonates among those with

early versus delayed cord clamping in terms of:

a. Maternal age, civil status, education
b. Maternal weight
c. BMI
d. Iron supplementation
e. Pre-delivery hemoglobin
f. Duration of breast feeding
g. Use of milk formula feeding
h. Multivitamins and minerals supplementation

3. To compare the venous hematocrit and mean corpuscular volume (MCV) of

neonates among those with cord clamping done within 10 seconds and those

after 3 minutes.

4. To compare the venous hematocrit and mean corpuscular volume (MCV) of

neonates with early versus delayed cord clamping done at 6 weeks and at 3

months post-natal.


4.1 Sample size Estimate:

In order to estimate a difference of at least 5% in the venous hematocrit

with a standard deviation of ±8% between early versus delayed (two-tailed test)

yielding a type 1 error of 10% and generating a power of 90%, with a variance of 2%,

the minimum sample required is 44 per arm.

Where n = is the sample size per group

Zα = a deviate corresponding to the α error rate
Zβ= a deviate corresponding to the β error rate
S2= variance
d= a difference to be detected

n= 44 per arm

4.2 Study Design: Randomized controlled trial comparing cord clamping done

at within 10 seconds (early) or delayed (3 minutes)

4.3 Setting: San Juan De Dios General Hospital . In this institution, the cord

clamping procedure is usually done within ± 10 seconds after birth.

4.4 Duration of Study: 10 –months

4.5 Primary Outcomes:

The primary endpoints of this study include the hematological and iron status of

infants at 6 weeks and at 3 months of age.

4.5 Inclusion Criteria of Mothers:

Women eligible to participate are there not in advanced labour (The Mother had

uncomplicated singleton pregnancies, Maternal gestational diabetes or (pre)eclampsia,

instrumental delivery, serious haemorrhage during pregnancy or delivery, the need for

early cord clamping – medical history of post-partum haemorrhage ).when admitted , or

did not have any of the following basic characteristics: planned delivery by caesarean

section; pregnancy of 36 weeks or less, or 42 weeks or more, as

established by the date of last menstrual period or estimated delivery date; or multiple


Exclusion Criteria : Women will be excluded if they had a diagnosis of any of the

following: medical conditions during the current pregnancy: preeclampsia or eclampsia

(also in any previous pregnancies), haemorrhage needing clinic or hospital admission,

placental abnormalities, anomalies or Down’s syndrome of the fetus, or had a diagnosis

at any time of diabetes (all types), hypertension, cardiopathies, or chronic renal disease

and hematological dyscrasias. Behavioural criteria for exclusion include those women

not planning to breastfeed for at least 6 months, if they smoked at all during

pregnancy, if unwilling to return for follow-up visits at the same hospital, or were

participating in another research study at the hospital. Written informed consent will be

obtained from

mothers who will be eligible and willing to participate.

4.6 Inclusion Criteria of Neonates

All live births with the following criteria: 1.) Term by sonographic as well as clinical

maturity rating 2.) Good APGAR scores 3.) informed parental consent

Exclusion Criteria : 1.) Those with jaundice at birth 2.) respiratory depression 3.)

infants born to mothers incurring severe maternal blood loss 3.) No parental consent

4.) those with ABO incompatibility 5.) major congenital abnormalities.

4.7 Random Sampling and Randomiztion

We will randomly assign participants to early or delayed clamping in blocks of

four using the random digit generator in Microsoft Excel. Numbered index cards

randomi with the assigned treatment will be sealed in corresponding numbered opaque

envelopes and ordered sequentially. Before delivery, the next envelope will be opened

by recruitment staff , who will inform the obstetrician and the pediatrician attending the

delivery of the assigned treatment. Study staff will not inform the mother of her

assignment; however, because of the nature of the intervention, the mothers may be

aware of which intervention they were randomized to. If a mother already

assigned to a treatment group later became ineligible (eg, method of delivery changed

to caesarean), her assigned treatment card will not be re-used. At all births, a staff

member is present to measure the time from the delivery of the infant’s shoulders to

the cord clamping. Obstetricians will be asked to maintain the infant at the level of the

mother’s uterus until the cord is clamped. In the early-clamping group, the staff

member informed the obstetrician when 10 second have passed and that the cord

should be clamped. In the delayed delayed clamping group, the staff member will

inform the

obstetrician of the passing time until 3 min (the intended clamping time). If the

physician feel that the infant or the mother needs attention that could not be given

while the infant remained attached to the umbilical cord, the cord will be clamped

before this time; however, original group assignment will not be changed. Exclusion

criteria applied after birth are low birth weight (<2500 g) and major congenital

malformations. Venous blood samples will be taken from the mother before delivery

and from the umbilical vein in the placenta immediately after its delivery. Obstetricians

will estimate the amount of maternal blood loss during the delivery and immediately

afterwards as normal, high, or severe. Infant weight and length will be measured

shortly after birth. Recruitment and follow-up staff were trained and standardized (a

formal process of repeated measurements to ensure comparability between individuals)

in standard anthropometric techniques. Capillary blood sample will be taken from the

infant’s heel. Before discharge from the hospital, study staff will record medical chart

information on complications or medical procedures for the infant and mother, and

completed a socioeconomic and demographic interview with the mother.

At 6 weeks and 3 months, the mother and her child will be scheduled for a

follow-up check-up. Hematocrit values will be obtained during these visits and data

collated. The routine well-baby check-up will follow. Subgroup analysis will be done to

adjust for effect of formula milk feeding and multivitamin and mineral used.


Since maternal nutrition, duration of breast feeding and use of formula feeding

are extraneous variables that can effect our study, a special subgroup analysis for

these factors will be performed to determine any statistical confounding.


Analyses will be done using intention-to-treat principle. All analyses will be

conducted using the SPSS version 14. Descriptive statistics include means and SD.

Testing for baseline homogeneity will be performed using Chi-square and independent

T-testing. Repeated ANOVA with post-hoc analysis will be done to determine significant

interaction between groups (early and late clamping) and venous hematocrit. A

regression analysis will be done to detect factors affecting hematocrit values of


All p-values of less than .05 will be considered statistically significant. Precision

will be expressed as 95% confidence intervals.

VI Ethical Considerations

The protocol will be submitted for Ethics Committee Review. The provisions of

the protocol conform to the Declaration of Helsinki and Ethics of Good Medical Research

Practice According to the World Health Organization.

Issues on confidentiality, autonomy and voluntary withdrawal from the study are

embodied in the informed and written consent.


1 World Health Organization. Care of the Umbilical Cord: A Review of the Evidence.
Geneva, Switzerland: World Health Organization; 1998:11–12.

2 Mercer JS. Current best evidence: a review of the literature on umbilical cord
clamping. J Midwifery Womens Health. 2001;46: 402–414

3 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;65:425–431

4 Michaelsen KF, Milman N, Samuelson G. A longitudinal study of iron status in

healthy Danish infants: effects of early iron status, growth velocity and dietary
factors. Acta Paediatr. 1995; 84:1035–1044

5 Ceriani Cernadas, J. M., Carroli, G., Pellegrini,L., Otan˜o, L., Ferreira, M., Ricci,
C., et al.(2006). The effect of timing of cord clamping on neonatal venous
hematocrit values and clinical outcome at term: A randomized, controlled
trial. Pediatrics, 117(4), e779–787.

6 Van Rheenen P, Brabin BJ. Late umbilical cord-clamping as an intervention for

reducing iron deficiency anaemia in term infantsin developing and industrialised
countries: a systematic review. Ann Trop Paediatr. 2004;24:3–16

7 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;81:745–750

8 Oh W, Blankenship W, Lind J. Further study of neonatal blood volume in relation

to placental transfusion. Ann Paediatr 1966; 207:147–59.

9 Usher R, Shephard M, Lind J. The blood volume of the newborn infant and
placental transfusion. Acta Paediatr 1963; 52: 497–512.

10 Institute of Medicine. Iron. Dietary reference intakes for vitamin A,vitamin K,

arsenic, boron, chromium, copper, iodine, iron,manganese, molybdenum, nickel,
silicon, vanadium, and zinc. Washington, DC: National Academy Press, 2001.


Group Mothers Age Civil Status

 Early Clamping  Single
 Delayed Clamping  Married
 Separated
Education Income Monthly Prenatal Check-Ups
 None  < 5T  No
 Elementary  5,001-10T  Yes
 High School  10,001-15T
 College  15,001 -20T Frequency
 Vocational  > 20T  Once
 Twice
 Thrice
 Complete
Iron Supplementation Pre-Delivery Hemoglobin Exclusive Breast Feeding ?
 Yes __________________  Yes
 No  No
Pre-Delivery Hematocrit Duration of breast feeding
__________________ _______________months

Use of Milk formula ? Multivitamins and minerals ? Comments:

 Yes  Yes
 No  No
If yes, since when ?_________ If yes, since when ?________


Sex Gestational Age Ballards Maturity Scoring

 Male  AGA
 Female  SGA _______________

Birth Weight=__________kg APGAR Score

1 min=___________
Birth Length=__________cm
5 mins=__________

Hematocrit at Birth Hematocrit at 6 weeks Hematocrit at 3 months

_________________ _________________ _________________

MCV at birth MCV at 6 weeks MCV at 3 months

________________ _________________ _________________


Items Cost Total

CBC determination
Office Supplies



May 19’ 2010

To : Rosendo R. Roque ,MD

Chairman, Dept of OB-Gyne

Cecilia Joyce M. Bascara ,MD

Training Officer, Dept of OB-Gyne

We, Jean Peter Siregar and Andre Inigo, third year pediatric residents of this
institution would like to ask for your kind permission and cooperation regarding our
studies :


HEMATOCRIT A Randomized Controlled Trial.

The protocol has passed the Research Ethics Committee of The Department and
this m will be submitted to the Hospital Research Committee. For details, a copy of the
protocol is attached per your disposal.

Hoping for a favorable response.


Jean Peter Siregar Andre Inigo, MD

3 Year Pediatrics Resident

San Juan De Dios Educational Foundation Inc

Approved by: Noted by:

Susan M.Andong, M.D. Leah G. Castro, M.D.

Training Officer-Department of Pediatrics Chair-Department of Pediatrics

Endorsed by:

Milagros Bacsain-Andres MD
Research Committee, Department of Pediatrics