ABSTRACT: The optimal timing for clamping the umbilical cord after birth has been a subject of controversy and debate. Although many randomized controlled trials in term and preterm infants have evaluated the benefits of delayed umbilical cord clamping versus immediate umbilical cord clamping, the ideal timing for cord clamping has yet to be established. Several systematic reviews have suggested that clamping the umbilical cord in all births should be delayed for at least 30–60 seconds, with the infant maintained at or below the level of the placenta because of the associated neonatal benefits, including increased blood volume, reduced need for blood transfusion, decreased incidence of intracranial hemorrhage in preterm infants, and lower frequency of iron deficiency anemia in term infants. Evidence exists to support delayed umbilical cord clamping in preterm infants, when feasible. The single most important clinical benefit for preterm infants is the possibility for a nearly 50% reduction in intraventricular hemorrhage. However, currently, evidence is insufficient to confirm or refute the potential for benefits from delayed umbilical cord clamping in term infants, especially in settings with rich resources.
Before the mid 1950s, the term “early clamping” was defined as umbilical cord clamping within 1 minute of birth, and “late clamping,” as umbilical cord clamping more than 5 minutes after birth. In a series of studies of blood volume changes after birth carried out by investigators in Sweden, the United States, and Canada, it was reported that in healthy term infants, more than 90% of blood volume was achieved within the first few breaths the infant took after birth (1). Because of these findings and the lack of specific recommendations regarding the optimal timing, the interval between birth and umbilical cord clamping began to be shortened. In most cases, umbilical cord clamping is performed within 15–20 seconds after birth, with the infant maintained at or below the level of the placenta. Although many randomized controlled trials of term and preterm infants have evaluated the benefits of immediate umbilical cord clamping versus delayed umbilical cord clamping (generally defined as umbilical cord clamping performed 30–60 seconds after birth) (2–26), the ideal timing for umbilical cord clamping has yet to be established and continues to be a subject of controversy and debate (21, 27–29).
Concerns exist regarding universally adopting delayed umbilical cord clamping. Delay in umbilical cord clamping may jeopardize timely resuscitation efforts, if needed, especially in preterm infants. However, because the placenta continues to perform gas exchange after delivery, sick and preterm infants are likely to benefit most from additional blood volume derived from a delay in umbilical cord clamping. Another concern has been raised that delay in umbilical cord clamping increases the potential for excessive placental transfusion, which can lead to neonatal polycythemia, especially in the presence of risk factors for fetal polycythemia, such as maternal diabetes, severe intrauterine growth restriction, and high altitude. Additionally, delayed umbilical cord clamping (with the infant placed at or below the level of the placenta) may be technically difficult in some circumstances. Another issue is that delayed umbilical cord clamping might interfere with attempts to collect cord blood for banking. However, the routine practice of umbilical cord clamping should not be altered for the collection of umbilical cord blood for banking (30).
Physiologic studies in term infants have shown that a transfer from the placenta of approximately 80 mL of blood occurs by 1 minute after birth, reaching approximately 100 mL at 3 minutes after birth (16, 31, 32). This additional blood can supply extra iron, amounting to 40–50 mg/kg of body weight. This extra iron, combined with body iron (approximately 75 mg/kg of body weight) present at birth in a full-term newborn, may help prevent iron deficiency during the first year of life (33).
Several systematic reviews have suggested that clamping the umbilical cord in all births should be delayed for at least 30–60 seconds, with the infant maintained at or below the level of the placenta because of the associated neonatal benefits (1, 21, 29, 33–35), including increased blood volume (2, 3, 13, 31, 36–40), reduced need for blood transfusion (17, 22, 41), decreased incidence of intracranial hemorrhage in preterm infants (10, 18, 29), and decreased frequency of iron deficiency anemia in term infants (7–9, 13, 24–26, 35–37, 40, 42).
In addition, a longer duration of placental transfusion after birth may be beneficial because this blood is enriched with immunoglobulins and stem cells, which provide the potential for improved organ repair and rebuilding after injury from disorders caused by preterm birth (39, 43). Although the magnitude of the benefits from enhanced placental stem cell transfusion has not been well studied, the other neonatal benefits have led investigators to consider revising umbilical cord clamping practice guidelines (4, 28, 40, 44–48).
The effect of delayed umbilical cord clamping on maternal outcomes has not been adequately studied. Some studies have shown no increase in the incidence of postpartum hemorrhage from delayed umbilical cord clamping. However, this remains a theoretic concern because blood flow through the spiral arteries and veins in a term uterus is approximately 600 mL/min. Concerns regarding maternal risks become particularly relevant in special circumstances in which the benefits of delayed umbilical cord clamping need to be balanced with the timely resuscitation of the woman (eg, in cases of hemorrhage from placenta previa or placental abruption after delivery of a preterm infant).
Clinical Trials in Term Infants
A 2008 Cochrane review assessed the effect of umbilical cord clamping in term infants on maternal and fetal outcomes in 11 clinical trials that involved 2,989 women and their infants (42). Reviewers found no significant differences in postpartum hemorrhage between the women whose infants underwent early umbilical cord clamping (within 1 minute after birth) and late umbilical cord clamping group (at least 1 minute after birth or after cessation of cord pulsation) in any of the five trials (2,236 women) that measured this outcome (relative risk [RR] for postpartum hemorrhage of 500 mL or more, 1.22; 95% confidence interval [CI], 0.96–1.55). The reviewers found that late umbilical cord clamping had positive and negative effects on neonatal outcomes. In five trials, which involved a total of 1,762 infants, a significant increase was noted in the need for phototherapy for jaundice after birth among infants in the late umbilical cord clamping group (RR, 1.69; 95% CI, 1.08–2.63). However, infants who underwent late umbilical cord clamping had significantly higher levels of hemoglobin (Hb) compared with infants in the early umbilical cord clamping group (weighted mean difference, 2.17 g/dL; 95% CI, 0.28–4.06). Infant ferritin levels remained higher in infants in the late umbilical cord clamping group compared with those in the early umbilical cord clamping group until 6 months (weighted mean difference, 11.8 micrograms per liter; 95% CI, 4.07–19.53).
Clinical Trials in Preterm Infants
In a systematic review of 10 trials of early umbilical cord clamping versus delayed umbilical cord clamping in 454 preterm infants (at less than 37 weeks of gestation), no statistically significant differences were found between the groups for cord blood pH (mean difference, 0.01; 95% CI, –0.03–0.05), Apgar scores (RR for 5-minute Apgar score of less than 8, 1.17; 95% CI, 0.62–2.2), and body temperature at admission (mean difference, 0.14 °C; 95% CI, –0.31–0.03) (2, 29). Benefits of delayed umbilical cord clamping included a reduced need for blood transfusions for low blood pressure (RR, 0.39; 95% CI, 0.18 to 0.85) and anemia (RR, 0.49; 95% CI, 0.31–0.81). No significant differences were noted for infant deaths (RR, 0.71; 95% CI, 0.3–1.69), but a significant reduction in the incidence of intraventricular hemorrhage with delayed umbilical cord clamping was reported by 7 of the 10 published studies (RR, 0.53; 95% CI, 0.35–0.79).
Another systematic review on this topic analyzed the results from 15 eligible studies (738 premature infants) (21). Infants were born between 24 weeks of gestation and 36 weeks of gestation. The maximum delay in umbilical cord clamping was 180 seconds. Delaying umbilical cord clamping was associated with fewer infants who required transfusion for anemia (seven trials, 392 infants; RR, 0.61; 95% CI, 0.46–0.81) and for low blood pressure (four trials with estimable data for 90 infants; RR, 0.52; 95% CI, 0.28–0.94); and less intraventricular hemorrhage (ultrasound diagnosis all grades) (10 trials, 539 infants; RR; 0.59; 95% CI, 0.41–0.85) compared with immediate umbilical cord clamping. For other outcomes (infant death, severe [grade 3–4] intraventricular hemorrhage, and periventricular leukomalacia), no clear differences were identified between groups; however, many trials were affected by incomplete reporting and wide confidence intervals. Outcome after discharge from the hospital was reported for one small study, and no significant differences were reported between the groups in mean Bayley II scores at age 7 months (corrected for gestation at birth and involved 58 children) (21).
Umbilical Cord Milking
One clinical trial and a secondary analysis from the same trial have compared “milking” of a 20-cm segment of the umbilical cord versus immediate umbilical cord clamping in preterm singleton infants born between 24 weeks of gestation and 28 weeks of gestation (49, 50). Significant findings in the clinical study included higher initial Hb concentration, higher mean systemic blood pressure, reduced need for blood transfusion, and higher urine output during the first 72 hours in the group that underwent umbilical cord milking compared with the group that underwent immediate umbilical cord clamping. The group that underwent umbilical cord milking also required a shorter duration of supplemental oxygen and mechanical ventilation. A 2011 randomized controlled trial of 58 preterm neonates (born at 24–32 6/7 weeks of gestation) randomized to receive either repeated milking of the umbilical cord (4 times) or delayed umbilical cord clamping of 30 seconds found that the two strategies had similar effects on Hb levels after birth (51). More studies are needed to evaluate the potential benefits and risks of umbilical cord milking, and at this time there is insufficient evidence to support umbilical cord milking in preterm infants.
Currently, insufficient evidence exists to support or to refute the benefits from delayed umbilical cord clamping for term infants that are born in settings with rich resources. Although a delay in umbilical cord clamping for up to 60 seconds may increase total body iron stores and blood volume, which may be particularly beneficial in populations in which iron deficiency is prevalent, these potential benefits must be weighed against the increased risk for neonatal phototherapy. In addition, no difference is apparent between infants who undergo early umbilical cord clamping versus those who undergo delayed umbilical cord clamping with respect to immediate birth outcomes, such as Apgar scores, umbilical cord pH, or respiratory distress caused by polycythemia (51). Although maternal outcomes have not been rigorously studied, the incidence of postpartum hemorrhage is reported to be similar between immediate umbilical cord clamping groups and late umbilical cord clamping groups.
However, evidence supports delayed umbilical cord clamping in preterm infants. As with term infants, delaying umbilical cord clamping to 30–60 seconds after birth with the infant at a level below the placenta is associated with neonatal benefits, including improved transitional circulation, better establishment of red blood cell volume, and decreased need for blood transfusion. The single most important clinical benefit for preterm infants is the possibility for a nearly 50% reduction in intraventricular hemorrhage. It is important to note that the timing of umbilical cord clamping should not be altered for the purpose of collecting umbilical cord blood for banking (30).
Although many randomized controlled trials that involved term infants and preterm infants have evaluated the benefits of delayed umbilical cord clamping versus immediate umbilical cord clamping, the ideal timing for umbilical cord clamping has yet to be established. Further studies also are needed to evaluate the optimal timing of umbilical cord clamping, the management of the third stage of labor in relation to umbilical cord clamping, and the timing of umbilical cord clamping in relation to the initiation of voluntary or assisted ventilation in the neonate. The ideal time for clamping the umbilical cord after cesarean delivery versus vaginal birth is an especially important area for future research. Premature infants, who may benefit most from delayed umbilical cord clamping, are more likely to be delivered by cesarean delivery because their mothers may have other medical and obstetric complications.
Large clinical trials are needed to investigate the effect of delayed umbilical cord clamping on infants delivered at less than 28 weeks of gestation. Further investigation is required to evaluate management of umbilical cord clamping in women with high-risk pregnancies whose infants are prone to develop polycythemia. The risks of umbilical cord milking remain unknown, and more studies are needed to compare milking of the umbilical cord with delayed umbilical cord clamping. The value of enhanced stem cell and plasma transfusion associated with delayed cord clamping with respect to immediate and long-term immunity, host defense, and repair is another important area for future research.
- Philip AG, Saigal S. When should we clamp the umbilical cord? Neoreviews 2004;5:e142–54.
- Aladangady N, McHugh S, Aitchison TC, Wardrop CA, Holland BM. Infants’ blood volume in a controlled trial of placental transfusion at preterm delivery. Pediatrics 2006;117:93–8.
- Baenziger O, Stolkin F, Keel M, von Siebenthal K, Fauchere JC, Das Kundu S, et al. The influence of the timing of cord clamping on postnatal cerebral oxygenation in preterm neonates: a randomized, controlled trial. Pediatrics 2007;119:455–9.
- Bell EF. When to transfuse preterm babies. Arch Dis Child Fetal Neonatal Ed 2008;93:F469–73.
- Ceriani Cernadas JM, Carroli G, Pellegrini L, Otano L, Ferreira M, Ricci C, et al. The effect of timing of cord clamping on neonatal venous hematocrit values and clinical outcome at term: a randomized, controlled trial. Pediatrics 2006;117:e779–86.
- Chaparro CM, Fornes R, Neufeld LM, Tena Alavez G, Eguia-Liz Cedillo R, Dewey KG. Early umbilical cord clamping contributes to elevated blood lead levels among infants with higher lead exposure. J Pediatr 2007;151:506–12.
- Chaparro CM, Neufeld LM, Tena Alavez G, Eguia-Liz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: a randomised controlled trial. Lancet 2006;367:1997–2004.
- 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;34:103–6.
- 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.
- Hofmeyr GJ, Bolton KD, Bowen DC, Govan JJ. Peri-ventricular/intraventricular haemorrhage and umbilical cord clamping. Findings and hypothesis. S Afr Med J 1988;73:104–6.
- Hofmeyr GJ, Gobetz L, Bex PJ, Van der Griendt M, Nikodem C, Skapinker R, et al. Periventricular/intraventricular hemorrhage following early and delayed umbilical cord clamping. A randomized controlled trial. Online J Curr Clin Trials 1993;Doc No 110.
- Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Placental transfusion: umbilical cord clamping and preterm infants. J Perinatol 2000;20:351–4.
- Jahazi A, Kordi M, Mirbehbahani NB, Mazloom SR. The effect of early and late umbilical cord clamping on neonatal hematocrit. J Perinatol 2008;28:523–5.
- Jaleel R, Deeba F, Khan A. Timing of umbilical cord clamping and neonatal haematological status. J Pak Med Assoc 2009;59:468–70.
- Kugelman A, Borenstein-Levin L, Riskin A, Chistyakov I, Ohel G, Gonen R, et al. Immediate versus delayed umbilical cord clamping in premature neonates born <35 weeks: a prospective, randomized, controlled study. Am J Perinatol 2007;24:307–15.
- Linderkamp O. Blood rheology in the newborn infant. Baillieres Clin Haematol 1987;1:801–25.
- McDonnell M, Henderson-Smart DJ. Delayed umbilical cord clamping in preterm infants: a feasibility study. J Paediatr Child Health 1997;33:308–10.
- Mercer J, Erickson-Owens D. Delayed cord clamping increases infants’ iron stores. Lancet 2006;367:1956–8.
- Mercer JS, McGrath MM, Hensman A, Silver H, Oh W. Immediate and delayed cord clamping in infants born between 24 and 32 weeks: a pilot randomized controlled trial. J Perinatol 2003;23:466–72.
- Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006;117:1235–42.
- Rabe H, Diaz-Rossello JL, Duley L, Dowswell T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD003248. DOI: 10.1002/14651858.CD003248.pub3.
- Rabe H, Wacker A, Hulskamp G, Hornig-Franz I, Schulze-Everding A, Harms E, et al. A randomised controlled trial of delayed cord clamping in very low birth weight preterm infants. Eur J Pediatr 2000;159:775–7.
- Ultee CA, van der Deure J, Swart J, Lasham C, van Baar AL. Delayed cord clamping in preterm infants delivered at 34 36 weeks’ gestation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2008;93:F20–3.
- van Rheenen P, Brabin BJ. Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: a systematic review. Ann Trop Paediatr 2004;24:3–16.
- van Rheenen P, de Moor L, Eschbach S, de Grooth H, Brabin B. Delayed cord clamping and haemoglobin levels in infancy: a randomised controlled trial in term babies. Trop Med Int Health 2007;12:603–16.
- van Rheenen PF, Gruschke S, Brabin BJ. Delayed umbilical cord clamping for reducing anaemia in low birthweight infants: implications for developing countries. Ann Trop Paediatr 2006;26:157–67.
- Mercer JS, Skovgaard RL. Neonatal transitional physiology: a new paradigm. J Perinat Neonatal Nurs 2002;15:56–75.
- Oh W. Timing of umbilical cord clamping at birth in full-term infants. JAMA 2007;297:1257–8.
- Rabe H, Reynolds G, Diaz-Rossello J. A systematic review and meta-analysis of a brief delay in clamping the umbilical cord of preterm infants. Neonatology 2008;93:138–44.
- Umbilical cord blood banking. ACOG Committee Opin-ion No. 399. American College of Obstetricians and Gynecologists. Obstet Gynecol 2008;111:475–7.
- 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;81:745–50.
- Yao AC, Lind J. Effect of early and late cord clamping on the systolic time intervals of the newborn infant. Acta Paediatr Scand 1977;66:489–93.
- Pisacane A. Neonatal prevention of iron deficiency. BMJ 1996;312:136–7.
- Eichenbaum-Pikser G, Zasloff JS. Delayed clamping of the umbilical cord: a review with implications for practice. J Midwifery Womens Health 2009;54:321–6.
- Hutton EK, Hassan ES. Late vs early clamping of the umbilical cord in full-term neonates: systematic review and meta-analysis of controlled trials. JAMA 2007;297:1241–52.
- Emhamed MO, van Rheenen P, Brabin BJ. The early effects of delayed cord clamping in term infants born to Libyan mothers. Trop Doct 2004;34:218–22.
- 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;39:130–5.
- Kinmond S, Aitchison TC, Holland BM, Jones JG, Turner TL, Wardrop CA. Umbilical cord clamping and preterm infants: a randomised trial. BMJ 1993;306:172–5.
- Levy T, Blickstein I. Timing of cord clamping revisited. J Perinat Med 2006;34:293–7.
- van Rheenen PF, Brabin BJ. A practical approach to timing cord clamping in resource poor settings. BMJ 2006;333:954–8.
- Strauss RG, Mock DM, Johnson K, Mock NI, Cress G, Knosp L, et al. Circulating RBC volume, measured with biotinylated RBCs, is superior to the Hct to document the hematologic effects of delayed versus immediate umbilical cord clamping in preterm neonates. Transfusion 2003;43:1168–72.
- McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database of Systematic Reviews 2008, Issue 2. Art. No.: CD004074. DOI: 10.1002/14651858.CD004074.pub2.
- Sanberg PR, Park DH, Borlongan CV. Stem cell transplants at childbirth. Stem Cell Rev 2010;6:27–30.
- Coggins M, Mercer J. Delayed cord clamping: advantages for infants. Nurs Womens Health 2009;13:132–9.
- Hutchon DJ. Delayed cord clamping may also be beneficial in rich settings. BMJ 2006;333:1073.
- Philip AG. Delayed cord clamping in preterm infants. Pediatrics 2006;117:1434–5.
- Rabe H, Alvarez JR, Lawn C, Seddon P, Amess PN. A management guideline to reduce the frequency of blood transfusion in very-low-birth-weight infants. Am J Perinatol 2009;26:179–83.
- Weeks A. Umbilical cord clamping after birth. BMJ 2007;335:312–3.
- Hosono S, Mugishima H, Fujita H, Hosono A, Minato M, Okada T, et al. Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks’ gestation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2008;93:F14–9.
- Hosono S, Mugishima H, Fujita H, Hosono A, Okada T, Takahashi S, et al. Blood pressure and urine output during the first 120 h of life in infants born at less than 29 weeks’ gestation related to umbilical cord milking. Arch Dis Child Fetal Neonatal Ed 2009;94:F328–31.
- Rabe H, Jewison A, Alvarez RF, Crook D, Stilton D, Bradley R, et al. Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Brighton Perinatal Study Group. Obstet Gynecol 2011;117:205–11.