By Ahizechukwu C. Eke, MD, PhD, MPH
Assistant Professor in Maternal Fetal Medicine, Division of Maternal Fetal Medicine, Department of Gynecology & Obstetrics, Johns Hopkins University School of Medicine, Baltimore
SYNOPSIS: Delayed umbilical cord clamping at the time of delivery resulted in higher mean hematocrit concentrations, with no significant maternal or neonatal complications when compared to immediate umbilical cord clamping.
SOURCE: Ofojebe CJ, Eleje GU, Ikechebelu JI, et al. A randomized controlled clinical trial on peripartum effects of delayed versus immediate umbilical cord clamping in term newborns. Eur J Obstet Gynecol Reprod Biol 2021 Jul; 262:99-104. doi: 10.1016/j.ejogrb.2021.04.038.
Immediate clamping of the umbilical cord following vaginal and cesarean deliveries was a common practice for decades, until the early 2000s, when practice began to shift toward delayed cord clamping because of the benefits of improved hematocrit and ferritin concentrations, increased stored iron, and reduced risk of anemia in neonates with delayed umbilical cord clamping.1 Although studies have demonstrated polycythemia in fetuses with delayed cord clamping, the polycythemia was transient and benign, and did not place fetuses at an increased risk of neonatal jaundice.1,2 In addition, no significant maternal or neonatal complications have been demonstrated with delayed umbilical cord clamping when compared to immediate cord clamping.3,4
Following delivery of the neonate, blood flow continues from the placenta to the fetus via the umbilical vessels, a condition known as placental transfusion.5 Physiological studies have demonstrated transfer of blood from the placenta to the neonate of approximately 80 mL of blood at one minute following delivery, reaching approximately 100 mL at three minutes of delivery.5,6 Therefore, delayed umbilical cord clamping provides sufficient time for the physiologic transition from fetal to neonatal life, and might be responsible for the significant reductions in intraventricular hemorrhage and necrotizing enterocolitis in neonates following delivery.7 However, a recent Cochrane review demonstrated there is insufficient evidence to show what the best delayed umbilical cord interval (in minutes) should be for optimal maternal and fetal outcomes.1 Therefore, Ofojebe and colleagues evaluated the effect of delayed umbilical cord clamping on neonatal hemoglobin level and serum bilirubin in term newborns.8
This was a randomized controlled clinical trial at a single tertiary center, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra state, Nigeria, between
July 1, 2019, and Sept. 30, 2020. Women with singleton pregnancies in labor at a gestational age from 37w0d to 42w0d and having vaginal deliveries were included.8 Exclusion criteria included women with chronic medical disease, such as human immunodeficiency virus I and II, diabetes mellitus, and rhesus isoimmunization, participants at increased risk of postpartum hemorrhage, preeclampsia, prolonged rupture of fetal membranes, participants with congenitally malformed fetuses, and those whose newborns had fetal asphyxia.8 The primary outcome measures included mean hemoglobin and bilirubin levels of the newborn (at birth and 48 hours after birth). Secondary outcome measures included incidence of maternal postpartum hemorrhage after intervention, neonatal polycythemia, anemia, need for phototherapy, and proportion of newborns with respiratory symptoms.8
Participants were randomized to an immediate vs. a delayed cord clamping group. The intervention in the delayed cord clamping group consisted of delay in clamping the cord for 60 seconds, while in the immediate cord clamping group the cord was clamped within 15 seconds after delivery. Following clamping and cutting of the cord, 3 mL of cord blood was collected for hemoglobin and bilirubin estimation. A sample size of at least 102 women per group was sufficient to demonstrate statistically significant differences between the immediate umbilical cord clamping and the delayed cord clamping groups based on a baseline mean hemoglobin of 14.5 g/dL in the immediate umbilical cord clamping group (standard deviation of 2.4 g/dL), assuming 90% power, a type 1 error rate of 5%, and a 20% attrition rate.
A total of 237 women were assessed for eligibility during the study period; 204 were eligible. Of these 204 women, 102 newborns were randomized into each group. None were lost to follow-up. Participants in both groups had similar socio-demographic and clinical characteristics.8 The mean birth weight for the delayed clamping group was 3.21 ± 0.19 kg, while that of immediate umbilical clamping group was 3.24 ± 0.27 kg; P = 0.360. There was a statistically significant difference in the mean cord blood hemoglobin at birth between the delayed clamping group and the immediate cord clamping group (15.65 ± 0.29 g/dL vs. 15.25 ± 0.48 g/dL; P < 0.001). Similarly, there was a statistically significant difference in the mean blood hemoglobin at 48 hours after birth between the delayed clamping group and that of the immediate cord clamping group (15.51 ± 1.71 g/dL vs. 15.16 ± 2.27 g/dL; P < 0.001).8 Cord blood bilirubin concentration at birth and mean infant bilirubin concentration at 48 hours after birth were not significantly different between the two groups. There was no statistically significant difference in the frequency of the secondary outcomes, notably postpartum hemorrhage (P = 0.653), neonatal jaundice (P = 0.856), and the need for phototherapy (P = 0.561). None of the infants had respiratory symptoms, polycythemia, or anemia during the study.8
COMMENTARY
Typically, active management of the third stage of labor involved the use of uterotonics, early clamping of the umbilical cord, and controlled cord traction to expedite placental delivery, with the aim of reducing blood loss. A Cochrane systematic review demonstrated that active management of labor resulted in a reduction in the average risk of primary hemorrhage at time of birth (more than 1,000 mL; relative risk [RR], 0.34; 95% confidence interval [CI], 0.14-0.87) and maternal hemoglobin less than 90 g/L following delivery (RR, 0.50; 95% CI, 0.30-0.83).9 Several other studies have demonstrated similar findings. However, immediate clamping of the umbilical cord has fallen out of favor because it can result in decreased neonatal iron stores, low birthweight, and increased risk of neonatal anemia.10
The optimal timing for umbilical cord clamping is unclear. Ofojebe et al defined immediate cord clamping as cord clamping done within 15 seconds after delivery and delayed cord clamping at 60 seconds post-delivery, but many other studies define immediate and delayed cord clamping as cord clamping done within 30 seconds of birth and until at least two minutes after delivery, respectively.8 These have important implications for clinical practice, since the time limit for immediate vs. delayed cord clamping can affect neonatal iron stores, ferritin, and birthweight. A systematic review and meta-analysis of randomized controlled clinical trials demonstrate that delaying clamping for at least two minutes is beneficial to fetuses from birth until approximately 1 year of age.11 The American College of Obstetricians and Gynecologists (ACOG), the International Federation of Gynecology and Obstetrics, and the World Health Organization (WHO) no longer recommend immediate cord clamping as a component of active management of labor.12 The WHO states that “delayed cord clamping (performed after one to three minutes after birth) is recommended for all births while initiating simultaneous essential newborn care. Early cord clamping (less than one minute after birth) is not recommended unless the neonate is asphyxiated and needs to be moved immediately for resuscitation.”13
Except for infants who require immediate neonatal resuscitation, the current recommendation by ACOG and the American Academy of Pediatrics is for delayed umbilical cord clamping for at least 30 to 60 seconds after birth (vaginal and cesarean deliveries) in all vigorous term and preterm neonates.12,14
REFERENCES
- Rabe H, Gyte GM, Díaz-Rossello JL, Duley L. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev 2019;9:CD003248.
- Mercer JS, Erickson-Owens DA, Collins J, et al. Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: A randomized controlled trial. J Perinatol 2017;37:260-264.
- McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. Cochrane Database Syst Rev 2013;2013:CD004074.
- Andersson O, Hellström-Westas L, Andersson D, et al. Effects of delayed compared with early umbilical cord clamping on maternal postpartum hemorrhage and cord blood gas sampling: A randomized trial. Acta Obstet Gynecol Scand 2013;92:567-574.
- Yao AC, Lind J. Placental transfusion. Am J Dis Child 1974;127:128-141.
- 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.
- Lodha A, Shah PS, Soraisham AS, et al. Association of deferred vs immediate cord clamping with severe neurological injury and survival in extremely low-gestational-age neonates. JAMA Netw Open 2019;2:e191286.
- Ofojebe CJ, Eleje GU, Ikechebelu JI, et al. A randomized controlled clinical trial on peripartum effects of delayed versus immediate umbilical cord clamping on term newborns. Eur J Obstet Gynecol Reprod Biol 2021;262:99-104.
- Begley CM, Gyte GM, Devane D, et al. Active versus expectant management for women in the third stage of labour. Cochrane Database Syst Rev 2019;2:CD007412.
- Bienstock JL, Eke AC, Hueppchen NA. Postpartum hemorrhage. N Engl J Med 2021;384:1635-1645.
- 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;297:1241-1252.
- American College of Obstetricians and Gynecologists' Committee on Obstetric Practice. Delayed umbilical cord clamping after birth: ACOG Committee Opinion, Number 814. Obstet Gynecol 2020;136:e100-e106.
- Tunçalp O, Souza JP, Gülmezoglu M, World Health Organization. New WHO recommendations on prevention and treatment of postpartum hemorrhage. Int J Gynaecol Obstet 2013;123:254-256.
- [No authors listed]. Delayed umbilical cord clamping after birth. Pediatrics 2017;139:e20170957.
