Early versus delayed umbilical cord clamping in preterm infants

 

Characteristics of included studies [ordered by study ID]

Hofmeyr 1988

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Methods	Randomized controlled trial, randomization cards, stratified by birthweight < 1500 g.
Participants	38 infants < 35 weeks. Exclusions: nil.
Interventions	Control: cord clamping immediately after birth. Intervention 1: cord camping delayed for 60 s Intervention 2: cord clamping delayed for 60 s and ergometrine given at delivery.
Outcomes	Primary outcome: cerebral Ultrasound 6-72 hours after birth. Secondary outcomes: Apgar scores, birthweight, systolic blood pressure at 5 minutes, cord blood gas, death.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Hofmeyr 1993

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Methods	Randomized controlled trial, randomized sealed cards.
Participants	86 infants < 2000 g. Exclusion: cord around the neck.
Interventions	Control group: cord clamped immediately. Intervention: cord clamping time 60-120 s, infant held at the level of the uterus for vaginal deliveries, infant held above the level of the uterus for caesarean section (on the mothers' thighs).
Outcomes	Primary outcome: cerebral ultrasound at 24 h. Secondary outcome: Apgar score, cord-pH.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Kinmond 1993

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Methods	Randomized controlled trial, sealed envelopes, stratification not given.
Participants	36 infants > 27 to < 33 weeks' gestation, vaginal delivery. Exclusions: haemolytic disease, major congenital malformations.
Interventions	Regulated group: positioning 20 cm below the introitus and cord clamped at 30 s. Non-regulated group: time to cord clamping recorded, management at the attendant's discretion.
Outcomes	Primary outcome: initial packed red cell volume, peak serum bilirubin, transfusion requirement, respiratory impairment, arterial-alveolar oxygen ratio, duration of oxygen.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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McDonnell 1997

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Methods	Randomized controlled trial, randomization by sealed opaque envelope, stratified by vaginal or caesarean section, 26 to 29 weeks, 30 to 33 weeks.
Participants	46 infants 26 to 33 weeks, vaginal or caesarean section, single or multiple pregnancies. Exclusions: severe fetal distress, IUGR with abnormal umbilical Doppler waveforms, fetal hydrops, fetal malformations, Rhesus incompatibility.
Interventions	Control group: cord clamped immediately. Intervention group: cord clamped at 30 s, infant positioned between legs of the mother, Syntocinon at birth of the infant.
Outcomes	Primary outcome: haematocrit at 4 h. Secondary outcomes: Apgar score, temperature on admission, requirement for ventilation, oxygen, surfactant. peak serum bilirubin, inotropic support, cerebral ultrasound, blood transfusion, death.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Nelle 1998

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Methods	Randomized controlled trial. Randomization by sealed opaque envelopes.
Participants	19 infants < 1500 g. Born by caesarean section.
Interventions	Control: cord clamped immediately after birth. Intervention: cord clamping after 30 s and positioning of the infant 30 cm below placenta.
Outcomes	Primary outcomes: mean arterial blood pressure, left ventricular output, mean cerebral blood flow velocity, haemoglobin, haematocrit, systemic and cerebral haemoglobin transport, volume expansion during the first 24 h.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Unclear	B - Unclear

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Oh 2002

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Methods	Randomized controlled trial. Randomization method by sealed opaque envelopes.
Participants	Infants 24-28 weeks.
Interventions	Control group: immediate cord clamping < 5 s. Intervention: delayed cord clamping 30-45 s.
Outcomes	Primary outcome: haematocrit at 4 h, Secondary outcomes: resuscitation, Apgar score, blood pressure during the first 12 h, intraventricular haemorrhage, necrotizing enterocolitis, retinopathy of prematurity, late onset sepsis, patent ductus arteriosus, blood transfusions.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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Rabe 2000

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Methods	Randomized controlled trial, opaque sealed envelopes.
Participants	40 infants < 33 weeks. Exclusions: multiple pregnancies, Rhesus incompatibility, fetal hydrops, congenital malformation, Apgar < 3 at 0 minutes.
Interventions	Control group: cord clamping at 20 s. Intervention: cord clamping at 45 s and positioning of the infant below the level of placenta, if possible, oxytocin at delivery of the first shoulder.
Outcomes	Primary outcome: number of blood transfusions during first 6 weeks of life. Secondary outcomes: Apgar score, temperature on admission, blood pressure at 1, 4 and 24 h, volume resuscitation during first 24 h, inotropic support, degree of respiratory distress, intraventricular haemorrhage, patent ductus arteriosus, phototherapy.
Notes
Risk of bias
Item	Authors' judgement	Description
Allocation concealment?	Yes	A - Adequate

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 h: hours
IUGR: intrauterine growth restriction
s: seconds

 

Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Aitchison	Trial plan only. No data recorded with this citation.
Frank 1967	This was a non-randomised study in which delayed cord clamping was defined as that performed after the second breath.
Ibrahim 2000	Randomized trial with adequate concealment. The intervention consisted of a delay in cord clamping of 20 seconds. Control infants had their cord clamped immediately. The study was excluded for the reason that the intervention group at a cord clamping time of less than 30 seconds. Delay of cord clamping was defined in the protocol for this review to be of at least 30 seconds duration.
Narendra 1998	Abstract only, further details on patients and study not available from the authors.
Saigal 1972	Sequential allocation procedure, which is not a randomized trial.
Saigal 1977	Sequential allocation procedure, which is not a randomized trial.
Spears 1966	Randomisation procedure was unclear. Gestational age of the low birth eight infants was not given.
Strauss 2003	Even though the title states "delayed versus immediate cord clamping", the intervention in delayed group less than 30 weeks' gestation consisted of harvesting and retransfusion of placental blood. No separate data are given for the group of 31 to 36 weeks' gestation.
Taylor 1963	Inadequate randomization. Largely term infants.

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Characteristics of ongoing studies [ordered by study ID]

Holland 1998

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Trial name or title	Placento-fetal (autologous) Transfusion at birth in infants born preterm: a randomized, controlled trial.
Methods
Participants	Infants < 33 weeks' gestation.
Interventions	Positioning of the infant below the placenta as far as possible. Vaginal delivery: delay of cord clamping 40 to 90 seconds. Caesarean section: cord clamping 40 to 90 seconds after syntocinon.
Outcomes	Primary outcome: median arterial/alveolar PO2 ratio over the first 24 hours of life. Secondary outcome: a. CRIB score b. RCV c. Transfusion requirements.
Starting date	1998
Contact information	BM Holland Queen Mother's Hospital Glasgow G3 8SH
Notes	Trial completed in 2001

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Mercer 2004

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Trial name or title	Randomized controlled trial of delayed cord clamping in infants born between 24 and 31 +6/7 weeks' gestation.
Methods
Participants	Infants between 24 and 31 +6/7 weeks' gestation stratified into 2 groups: 24 to 27 +6/7 and 28 to 31 +6/7 weeks' gestation.
Interventions	Positioning of infant 10-15 inches below mother's introitus at vaginal delivery or 10-15 inches below the level of the placenta at caesarean section, cord clamping time at 30 to 45 seconds.
Outcomes	Primary outcome: Chronic lung disease, NEC, medical morbidity at 7 months corrected age and neurodevelopmental outcome at 18 months corrected age.
Starting date	2003
Contact information	J Mercer Women and Children's Hospital Providence, Rhode Island USA
Notes	Trial ongoing

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 CRIB: Critical Risk Index for Babies
NEC: necrotising enterocolitis
RCV: red cell volume

 

Comparison 1. Early versus delayed cord clamping

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Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Death of the baby	6	278	Risk Ratio (M-H, Fixed, 95% CI)	1.05 [0.41, 2.73]
2 Transfused for anaemia	3	111	Risk Ratio (M-H, Fixed, 95% CI)	2.01 [1.24, 3.27]
3 Transfused for low blood pressure	2	58	Risk Ratio (M-H, Fixed, 95% CI)	2.58 [1.17, 5.67]
4 Number of transfusions	3	98	Mean Difference (IV, Fixed, 95% CI)	1.28 [0.58, 1.98]
5 Haematocrit at birth or 1 hour (%)	3	112	Mean Difference (IV, Fixed, 95% CI)	-3.21 [-5.62, -0.80]
6 Haematocrit at 4 hours of life (%)	4	134	Mean Difference (IV, Fixed, 95% CI)	-5.40 [-7.28, -3.52]
8 Serum bilirubin peak (mmol/litre)	3	111	Mean Difference (IV, Fixed, 95% CI)	-21.49 [-38.04, -4.94]
9 Hyperbilirubinemia (treated)	1	39	Risk Ratio (M-H, Fixed, 95% CI)	0.95 [0.58, 1.56]
11 Inotropics for low blood pressure	3	118	Risk Ratio (M-H, Fixed, 95% CI)	2.17 [0.51, 9.12]
12 Patent ductus arteriosus	3	118	Risk Ratio (M-H, Fixed, 95% CI)	0.79 [0.36, 1.72]
13 Intraventricular haemorrhage	5	225	Risk Ratio (M-H, Fixed, 95% CI)	1.74 [1.08, 2.81]
14 Severe intraventricular haemorrhage	3	161	Risk Ratio (M-H, Fixed, 95% CI)	0.86 [0.15, 4.75]
15 Periventricular leucomalacia	1	31	Risk Ratio (M-H, Fixed, 95% CI)	0.31 [0.01, 7.15]
16 Respiratory distress syndrome	2	75	Risk Ratio (M-H, Fixed, 95% CI)	0.83 [0.59, 1.15]
17 Severe respiratory distress syndrome	1	39	Risk Ratio (M-H, Fixed, 95% CI)	1.27 [0.33, 4.93]
18 Ventilated for respiratory distress syndrome	3	121	Risk Ratio (M-H, Fixed, 95% CI)	0.91 [0.65, 1.28]
19 Surfactant treatment	2	85	Risk Ratio (M-H, Fixed, 95% CI)	0.78 [0.34, 1.79]
21 Oxygen supplementation at 28 days	1	36	Risk Ratio (M-H, Fixed, 95% CI)	6.3 [0.35, 113.81]
22 Oxygen supplementation at 36 weeks	2	65	Risk Ratio (M-H, Fixed, 95% CI)	0.97 [0.35, 2.69]
23 Necrotizing enterocolitis	2	72	Risk Ratio (M-H, Fixed, 95% CI)	2.08 [0.52, 8.37]
24 Cord pH	3	123	Mean Difference (IV, Fixed, 95% CI)	0.01 [-0.03, 0.05]
25 Apgar score at 5th minute < 8	3	161	Risk Ratio (M-H, Fixed, 95% CI)	1.17 [0.62, 2.20]
26 Temperature on admission (degrees Celsius)	1	39	Mean Difference (IV, Fixed, 95% CI)	-0.20 [-0.43, 0.03]

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