1. Objectives

To determine the effects of early cord clamping compared with late cord clamping after birth on maternal and neonatal outcomes.

2. How studies were identified

The following databases were searched in February 2013:

• Cochrane Pregnancy and Childbirth Group’s Trials Register
• CENTRAL (The Cochrane Library)
• MEDLINE
• EMBASE

The Cochrane Pregnancy and Childbirth Group’s Trials Register contains trials handsearched from 30 journals and the proceedings of major conferences, and weekly alerts from a further 44 journals

3. Criteria for including studies in the review

3.1 Study type

Randomized controlled trials

3.2 Study participants

Women who gave birth to a term infant (≥37 completed weeks’ gestation) where clamping of the umbilical cord was applied

(Caesarean sections were included; however, preterm births, multiple births and breech presentations were excluded)

3.3 Interventions

• Early cord clamping, within 60 seconds of birth
• Later/delayed cord clamping, more than one minute after birth or when cord pulsation has ceased

3.4 Primary outcomes

• Severe postpartum haemorrhage (blood loss ≥1000 mL)
• A composite outcome of maternal death or severe morbidity (major surgery, organ failure, intensive care unit (ICU) admission)
• Neonatal mortality

Secondary outcomes for the mother included: maternal death, major surgery, organ failure, ICU admission (considered as separate outcomes); postpartum haemorrhage ≥500 mL; length of third stage of labour; mean blood loss; manual removal of the placenta; blood transfusion; use of therapeutic uterotonics; additional treatment for postpartum haemorrhage; adverse effects (e.g., vomiting, pyrexia, shortness of breath); postnatal anaemia; thrombo-embolic events; and cost

Secondary outcomes for the infant included: birth weight; Apgar score less than seven at five minutes post-birth; admission to special care baby nursery or neonatal intensive care unit; respiratory distress; hypoxia; jaundice requiring phototherapy; clinical jaundice; cord haemoglobin concentration; not breastfed at discharge; neonatal and infant anaemia up to four to six months post-birth; neonatal and infant haemoglobin concentrations; neonatal and infant haematocrit; neonatal and child neurodevelopmental outcome; polycythaemia (haematocrit >65%); neonatal and infant ferritin concentrations; and symptoms of infection

4. Main results

4.1 Included studies

Fifteen randomized controlled trials, enrolling 3911 women, were included in this review:

• Participants were generally healthy women expected to give birth vaginally, although three studies included data for caesarean section birth
• In most studies, early cord clamping was performed within 15 seconds of birth
• Timing of late cord clamping was more variable, ranging from one to five minutes post-birth, or following cessation of cord pulsing or descent of the placenta

4.2 Study settings

• Argentina, Australia, Canada (2 studies), India (2 studies), Iran, Libya, Mexico, Saudi Arabia, Sweden, the United Kingdom of Great Britain and Northern Ireland (2 studies), the United States of America, and Zambia

4.3 Study settings

How the data were analysed
Early cord clamping (within 60 seconds of birth) was compared with delayed cord clamping (> one minute post-birth). Dichotomous outcomes were analysed as average risk ratios (RR) and 95% confidence intervals (CI), and for continuous outcomes, the mean difference (MD) was used.

The following subgroup analyses were planned:

• Whether or not uterotonics were used to stimulate the uterus to contract
• Whether or not the neonate was held above or below the abdomen before cord clamping
• By degree of selection bias

There were insufficient data to conduct subgroup analyses by neonate placement or by selection bias.

Results
Severe postpartum haemorrhage ≥1000 mL
In five trials including 2066 women, no significant difference in the risk of postpartum haemorrhage was found between early versus late cord clamping, RR 1.04, 95% CI [0.65 to 1.65], p=0.88. There were no significant differences between subgroups depending on administration of uterotonics.

Maternal death or severe morbidity
No included studies reported on maternal death or severe morbidity.

Neonatal death
Data on neonatal death was limited. In two studies of 381 women, four neonatal deaths were reported with no significant difference between early and late clamping groups (RR 0.37, 95% CI [0.04 to 3.41], p=0.38).

Maternal secondary outcomes
There were no significant differences between early and late cord clamping groups for postpartum haemorrhage ≥500 mL; mean blood loss; postpartum haemoglobin; length of third stage of labour; or requirement for blood transfusion, manual removal of the placenta, or therapeutic uterotonics. No data on other pre-specified maternal outcomes were reported in the included studies.

Neonatal secondary outcomes
No significant differences were found for Apgar score, admission to special care baby nursery or neonatal intensive care unit, respiratory distress, polycythaemia, breastfeeding status, neurodevelopmental outcome, or neonatal and child infection. While the number of infants with clinical jaundice was not different between groups, significantly fewer infants in the early cord clamping group required phototherapy for jaundice, RR 0.62, 95% CI [0.41 to 0.96], p=0.032 (7 trials/2324 infants).

Cord haemoglobin concentrations were significantly higher in the early clamping group (MD 0.41 g/dL, 95% CI [0.15 to 0.66], p=0.0017; 5 trials/696 infants), whereas newborn haemoglobin concentrations were lower (MD -2.17 g/dL, 95% CI [-4.06 to -0.28], p=0.025; 3 studies/671 infants). At 24 to 48 hours post-birth, the early cord clamping group also had significantly lower haemoglobin concentrations (MD -1.49 g/dL, 95% CI [-1.78 to -1.21], p<0.00001, 4 trials/884 infants). There were no significant differences between groups in haemoglobin concentrations or risk of infant anaemia at three to six months of age. In one trial including 180 infants, haematocrit was significantly lower in the early clamping group at 24 hours post-birth (MD -4.40%, 95% CI [-5.71 to -3.09], p<0.00001); however, the difference did not persist at three to five months of age. In one study which used a threshold of <45% haematocrit as an indicator of anaemia, more infants in the early clamping group were anaemic at six hours (RR 16.18, 95% CI [2.05 to 127.37], p=0.0082, 272 infants), and this effect persisted at 24 to 48 hours (RR 6.03, 95% CI [2.27 to 16.07], p=0.00032, 268 infants). Infants in the early clamping group were significantly more likely to have iron deficiency at three to six months than those in the late clamping group (RR 2.65, 95% CI [1.04 to 6.73], 5 trials/1152 infants; p=0.041). Mean birth weight was lower in the early cord clamping intervention group, MD -101.18 g, 95% CI [-157.59 to -44.76], p=00044 (12 trials/3139 infants).

5. Additional author observations*

Overall, the methodological quality of the trials included in this review was moderate to high, with no trials assessed as being at high risk of bias. While lack of blinding was unavoidable, knowledge of allocation among outcome assessors may have also affected judgement and clinical care. Seven studies reported blinding of data collection to reduce detection bias and nine of the 15 studies reported methods to conceal allocation at the point of randomization.

In agreement with other previous reviews and with current WHO guidelines recommending cord clamping between one to three minutes post-birth, delaying clamping of the umbilical cord was found to be beneficial overall for the infant in this review. The potential for adverse effects should be considered, however: if treatment for severe jaundice is not easily accessible, late cord clamping may not be optimal.

For some outcomes event rates were low, and future studies with adequate power should investigate maternal outcomes such as postpartum haemorrhage and longer-term infant outcomes such as neurodevelopment.