Summary of evidence

Maternal outcomes

The guideline development group – prevention and treatment of postpartum haemorrhage analysed data from a Cochrane review, which included maternal outcomes, specifically postpartum haemorrhage (20). In this recently updated review, five randomized controlled trials (>2000 women) included postpartum haemorrhage as the outcome in relation to umbilical cord clamping time (17). There were no significant differences in the rates of severe postpartum haemorrhage (>1000 mL) or postpartum haemorrhage (>500 mL) between groups with early or delayed umbilical cord clamping. In addition, no significant effect of umbilical cord clamping time was observed in the trials that evaluated the use of manual removal of the placenta (two trials, 1515 women), the need for blood transfusion (two trials, 1345 women), or the length of the third stage of labour (two trials, 1345 women) (17).

Neonatal outcomes (term and preterm infants)

The guideline development group working on the review of the evidence for basic neonatal resuscitation analysed various studies, including many included in the aforementioned Cochrane reviews on preterm and term infants (17, 18). Since additional studies are included in the most recent versions of these Cochrane reviews, a summary of the evidence is provided next. The guideline development group – neonatal resuscitation recommendations on cord clamping (2) discussed the evidence from this review.

Fifteen randomized controlled trials (738 infants) have evaluated the effects of umbilical cord clamping time in preterm neonates born predominantly in high-income countries (18). Outcomes studied among preterm infants included risk of mortality, incidence of necrotizing enterocolitis and intraventricular haemorrhage, need for blood transfusions for anaemia or low blood pressure, and hyperbilirubinemia. No studies in neonates with respiratory depression were identified and few studies measured respiratory outcomes. There was considerable heterogeneity between the included studies in the definition of “late” clamping time (from roughly 30 s to 180 s after birth) and positioning of the infant relative to the placenta or uterus before clamping. There was no difference in risk of mortality between preterm infants with delayed or early umbilical cord clamping (13 studies, 668 infants). Preterm infants with delayed umbilical cord clamping had a lower risk of necrotizing enterocolitis (5 trials, 241 infants) and intraventricular haemorrhage (10 trials, 539 infants). Seven randomized trials (392 infants) looked at the need for blood transfusions for anaemia or low blood pressure among preterm infants; on average, there was approximately a 39% reduction in the need for blood transfusion with delayed umbilical cord clamping. Delayed-clamped infants had significantly higher peak bilirubin concentrations as compared to early-clamped infants, in the seven trials (320 infants) reporting this outcome. There was no significant difference in treatment for jaundice between early- and delayed-clamped infants (three trials, 180 infants), though the treatment criteria probably differed between studies and were not always stated.

Fifteen randomized controlled trials have assessed the effects of umbilical cord clamping time in term infants from low-, middle- and high-income countries (17). Outcomes studied among term infants included neonatal mortality, admission to intensive care, haematological and iron status outcomes at birth and through to 6 months of age, polycythaemia, jaundice, and neurodevelopment. In most trials, early clamping occurred within 15 seconds of birth, while delayed clamping varied between 1 and 5 minutes after delivery, or at the end of umbilical cord pulsations. There was no difference in neonatal mortality (two trials, 241 infants), or rate of admission to intensive care (four trials, 1675 infants) between early- and delayed-clamped infants. Four studies (954 infants) looked at the risk of anaemia at 3–6 months of age among term infants and no significant difference was found in the rates of anaemia between the delayed- and early-clamping groups. Five trials of term infants (1152 infants) measured indicators of iron deficiency at 3–6 months of age. Infants with delayed clamping were significantly less likely to have iron deficiency than early-clamped infants, though there was high heterogeneity in this outcome, probably because of different measures/ definitions of iron deficiency, as well as the age at which it was assessed. Five trials (1025 infants) reported the effect of timing of umbilical cord clamping on the incidence of polycythaemia among term infants, with no difference between delayed and early umbilical cord clamping. Seven randomized controlled trials (2324 infants) examined the risk of receiving phototherapy for hyperbilirubinaemia following delayed umbilical cord clamping in term neonates. In the majority of the studies, the criteria used for phototherapy were not strictly defined. Delayed-clamped infants were significantly more likely to require phototherapy for jaundice, with a risk difference of <2% between early- and delayed-clamped infants. Only one study (365 infants) evaluated neurodevelopment in term infants, and found no significant effect of umbilical cord clamping time on the measures assessed at 4 months of age.

There were no randomized trials meeting the inclusion criteria set for the Cochrane review assessing alternative positions for the baby immediately at birth before clamping the umbilical cord (e.g. placed on the mother's abdomen versus held at the level of the vagina) (19). The criteria were set with the purpose of assessing whether gravity influences placental transfusion at vaginal and caesarean births. Since publication of this review in 2010, a multi-centre randomized controlled trial compared the amount of placental transfusion when the infant was placed on the mother's abdomen versus held at the level of the mother's vagina when delayed umbilical cord clamping occurred (21). The authors of the study reported that the position of the infant did not significantly affect the amount of blood transferred to the infant with delayed clamping.

The International Clinical Trials Registry Platform (ICTRP) (22) and Clinical Trials Registry (23) were searched (17 September 2014) for any ongoing or planned studies, using the search terms “umbilical cord clamping” and “umbilical cord milking”. Details of ongoing trials are presented in Annex 1. Duplicates were removed and completed studies were excluded. Twenty-six ongoing trials on cord clamping were identified. Sixteen of the trials propose to investigate the effect of delayed umbilical cord clamping on preterm infants, the majority of which are being conducted in the United States of America. In seven studies of preterm infants, placental transfusion will be made by milking the umbilical cord; three of these trials will aim to compare milking with delayed cord clamping. One trial of preterm infants aims to determine the combined effects of delayed cord clamping and neonatal resuscitation on placental transfusion. Ten studies on the effects of cord clamping time in term infants are planned or ongoing. One study aims to compare umbilical cord milking to delayed clamping, and two studies aim to look at neurodevelopment outcomes between early- and delayed-clamped infants. Two studies of term infants are investigating the effects of delayed clamping in infants born by caesarean section. The majority of the ongoing trials are expected to be finalized by 2016.