Skip to main content

Advertisement

SpringerLink
Log in

Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Despite advancement in medical care, Rh alloimmunisation remains a major cause of neonatal hyperbilirubinaemia, neuro-morbidity, and late-onset anaemia. Delayed cord clamping (DCC), a standard care now-a-days, is yet not performed in Rh-alloimmunised infants due to paucity of evidence. Hence, we randomised these infants of 28- to 41-week gestation to delayed cord clamping (N = 36) or early cord clamping (N = 34) groups. The primary outcome variable was venous packed cell volume (PCV) at 2 h of birth. The secondary outcomes were incidence of double volume exchange transfusion (DVET) and partial exchange transfusion (PET), duration of phototherapy (PT), functional echocardiography (parameters measured: superior vena cava flow, M-mode fractional shortening, left ventricular output, myocardial perfusion index, and inferior vena cava collapsibility) during hospital stay, and blood transfusion (BT) until 14 weeks of life. Neonates were managed as per unit protocol. The baseline characteristics of enrolled infants were comparable between the groups. The median (IQR) gestation and mean (SD) birth weight of enrolled infants were 35 (33–37) weeks and 2440 (542) g, respectively. The DCC group had a higher mean PCV at 2 h of life (48.4 ± 9.2 vs. 43.5 ± 8.7, mean difference 4.9% (95% CI 0.6–9.1), p = 0.03). However, incidence of DVET and PET, duration of PT, echocardiography parameters, and BT until 14 weeks of postnatal age were similar between the groups.

Conclusion: DCC in Rh-alloimmunised infants improved PCV at 2 h of age without significant adverse effects.

Trial registration: Clinical Trial Registry of India (CTRI), Ref/2016/11/012572 http://ctri.nic.in/Clinicaltrials, date of trial registration 19.12.2016, date of first patient enrolment 1 January 2017.

What is Known:

•Delayed cord clamping improves haematocrit, results in better haemodynamic stability, and decreases the need of transfusion in early infancy.

•However, due to lack of evidence, potential risk of hyperbilirubinaemia, and exacerbation of anaemia (following delayed cord clamping), early cord clamping is the usual norm in Rh-alloimmunised infantsinfants.

What is New:

•Delayed cord clamping in Rh-alloimmunised infants improves haematocrit at 2 h of life without any increase in incidence of serious adverse effects.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

Apgar:

Appearance, pulse, grimace, activity, respiration

ACA:

Anterior cerebral artery flow

DCC:

Delayed cord clamping

DVET:

Double volume exchange transfusion

PET:

Partial exchange transfusion

ECC:

Early cord clamping

EF:

Ejection fraction

FS:

Fractional shortening

IVRT:

Isovolumetric relaxation time

IVC:

Inferior vena cava

MCA:

Middle cerebral artery

PCV:

Packed cell volume

RBCs:

Red blood cells

SMA:

Superior mesenteric artery

SVC:

Superior vena cava

References

  1. Bhutani VK, Zipursky A, Blencowe H, Khanna R, Sgro M, Ebbesen F et al (2013) Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels. Pediatr Res 74:86–100

    Article  Google Scholar 

  2. Zipursky A, Paul VK (2011) The global burden of Rh disease. Arch Dis Child Fetal Neonatal Ed 96(2):F84–F85

    Article  Google Scholar 

  3. De Boer IP, Zeestraten ECM, Lopriore E, van Kamp IL, Kanhai HHH, Walther FJ (2008) Pediatric outcome in Rhesus hemolytic disease treated with and without intrauterine transfusion. Am J Obstet Gynecol 198(1):54.e1–54.e4

    Article  Google Scholar 

  4. al-Alaiyan S, al Omran A (1999) Late hyporegenerative anemia in neonates with rhesus hemolytic disease. J Perinat Med 27(2):112–115

    Article  CAS  Google Scholar 

  5. Burk CD, Malatack JJ, Ramsey G (1987) Misleading Rh phenotype and severe prolonged anemia in hemolytic disease of the newborn. Am J Dis Child 1960 141(7):712–713

    CAS  Google Scholar 

  6. Rabe H, Diaz-Rossello JL, Duley L, Dowswell T (2012) Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. In: The Cochrane Collaboration. Cochrane database of systematic reviews. Wiley, Chichester. https://doi.org/10.1002/14651858.CD003248.pub3. Accessed 19 June 2016

  7. McDonald SJ, Middleton P, Dowswell T, Morris PS (2013) Effect of timing of umbilical cord clamping of term infants on maternal and neonatal outcomes. In: The Cochrane Collaboration. Cochrane database of systematic reviews. Wiley, Chichester. https://doi.org/10.1002/14651858.CD004074.pub3. Accessed 19 June 2016

  8. Fogarty M, Osborn DA, Askie L, Seidler AL, Hunter K, Lui K, Simes J, Tarnow-Mordi W (2018) Delayed vs early umbilical cord clamping for preterm infants: a systematic review and meta-analysis. Am J Obstet Gynecol 218(1):1–18

    Article  Google Scholar 

  9. World Health Organization (2014) Nutrition for Health and Development, World Health Organization. Guideline: delayed umbilical cord clamping for improved maternal and infant health and nutrition outcomes. http://www.ncbi.nlm.nih.gov/books/NBK310511/. Accessed 21 Sept 2016

  10. Committee on Obstetric Practice (2017) Committee Opinion No. 684: delayed umbilical cord clamping after birth. Obstet Gynecol 129(1):e5–e10

    Article  Google Scholar 

  11. Wyllie J, Bruinenberg J, Roehr CC, Rüdiger M, Trevisanuto D, Urlesberger B (2015) European Resuscitation Council Guidelines for Resuscitation 2015. Resuscitation 95:249–263

    Article  Google Scholar 

  12. NRP Textbook of neonatal resuscitation. 7th edition. Elk Grove Village, IL: American Academy of Pediatrics; 2016

  13. Garabedian C, Rakza T, Drumez E, Poleszczuk M, Ghesquiere L, Wibaut B, Depoortere MH, Vaast P, Storme L, Houfflin-Debarge V (2016) Benefits of delayed cord clamping in red blood cell alloimmunization. Pediatrics. 137(3):e20153236

    Article  Google Scholar 

  14. Gupta R, Ramji S (2002) Effect of delayed cord clamping on iron stores in infants born to anemic mothers: a randomized controlled trial. Indian Pediatr 39(2):130–135

    PubMed  Google Scholar 

  15. Ramji S (2015) Delayed cord clamping and umbilical cord milking at birth. Indian Pediatr 52(9):749–749

    PubMed  Google Scholar 

  16. Dipak NK, Nanavati RN, Kabra NK, Srinivasan A, Ananthan A (2017) Effect of delayed cord clamping on hematocrit, and thermal and hemodynamic stability in preterm neonates: a randomized controlled trial. Indian Pediatr 54(2):112–115

    Article  Google Scholar 

  17. Rana A, Agarwal K (2017) Safety of delayed umbilical cord clamping in preterm neonates less than 34 weeks gestation. Indian J Pediatr 84(5):414–414

    Article  Google Scholar 

  18. Tarnow-Mordi W, Morris J, Kirby A, Robledo K, Askie L, Brown R, Evans N, Finlayson S, Fogarty M, Gebski V, Ghadge A, Hague W, Isaacs D, Jeffery M, Keech A, Kluckow M, Popat H, Sebastian L, Aagaard K, Belfort M, Pammi M, Abdel-Latif M, Reynolds G, Ariff S, Sheikh L, Chen Y, Colditz P, Liley H, Pritchard M, de Luca D, de Waal K, Forder P, Duley L, el-Naggar W, Gill A, Newnham J, Simmer K, Groom K, Weston P, Gullam J, Patel H, Koh G, Lui K, Marlow N, Morris S, Sehgal A, Wallace E, Soll R, Young L, Sweet D, Walker S, Watkins A, Wright I, Osborn D, Simes J, Australian Placental Transfusion Study Collaborative Group (2017) Delayed versus immediate cord clamping in preterm infants. N Engl J Med 377(25):2445–2455

    Article  Google Scholar 

  19. Mercer JS, Erickson-Owens DA, Collins J, Barcelos MO, Parker AB, Padbury JF (2017) Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial. J Perinatol Off J Calif Perinat Assoc 37(3):260–264

    CAS  Google Scholar 

  20. Agarwal R, Deorari A, Paul VK (2015) AIIMS protocols in neonatology, 1st edn. CBS Publishers and distributors, New Delhi

    Google Scholar 

  21. Skinner J, Alverson D, Hunter S (2000) Echocardiography for the neonatologist, 1st edn. Churchill Livingstone, London

    Google Scholar 

  22. Venkatnarayan K, Sankar MJ, Agarwal R, Paul VK, Deorari AK (2013) Phenobarbitone in Rh hemolytic disease of the newborn: a randomized double-blinded placebo-controlled trial. J Trop Pediatr 59(5):380–386

    Article  Google Scholar 

  23. Kc A, Rana N, Målqvist M, Jarawka Ranneberg L, Subedi K, Andersson O (2017) Effects of delayed umbilical cord clamping vs early clamping on anemia in infants at 8 and 12 months: a randomized clinical trial. JAMA Pediatr 171(3):264–270

    Article  Google Scholar 

  24. Andersson O, Hellström-Westas L, Andersson D, Domellöf M (2011) Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial. BMJ. 343:d7157

    Article  Google Scholar 

  25. Al-Tawil M, Abdel-Aal MR, Kaddah MA (2012) A randomized controlled trial on delayed cord clamping and iron status at 3–5 months in term neonates held at the level of maternal pelvis. Journal of Neonatal-Perinatal Medicine 5(4):319–326. https://doi.org/10.3233/NPM-1263112

  26. Strauss RG, Mock DM, Johnson KJ, Cress GA, Burmeister LF, Zimmerman MB et al (2008) A randomized clinical trial comparing immediate versus delayed clamping of the umbilical cord in preterm infants: short-term clinical and laboratory endpoints. Transfusion (Paris) 48(4):658–665

    Article  Google Scholar 

  27. Grajeda R, Pérez-Escamilla R, Dewey KG (1997) Delayed clamping of the umbilical cord improves hematologic status of Guatemalan infants at 2 mo of age. Am J Clin Nutr 65(2):425–431

    Article  CAS  Google Scholar 

  28. Polin RA, Fox WW, Abman SH, Rowitch DH, Benitz WE (2017) Fetal and neonatal physiology, vol 2, 5th edn. Elsevier, Philadelphia

    Google Scholar 

  29. Wang M, Mercer JS, Padbury JF (2018) Delayed cord clamping in infants with suspected intrauterine growth restriction. J Pediatr 201:264–268

    Article  Google Scholar 

  30. Nesheli HM, Esmailzadeh S, Haghshenas M, Bijani A, Moghaddam TG (2014) Effect of late vs early clamping of the umbilical cord (on haemoglobin level) in full-term neonates. JPMA J Pak Med Assoc 64(11):1303–1305

    PubMed  Google Scholar 

  31. Katheria AC, Brown MK, Faksh A, Hassen KO, Rich W, Lazarus D et al (2017) Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J Pediatr 187:313–317

    Article  Google Scholar 

  32. Ghirardello S, Crippa BL, Cortesi V, Di Francesco E, Consonni D, Colombo L, et al. (2018) Delayed cord clamping increased the need for phototherapy treatment in infants with ABO alloimmunization born by caesarean section: a retrospective study. Front Pediatr 6:241. https://doi.org/10.3389/fped.2018.00241

  33. McGlone L, Simpson JH, Scott-Lang C, Cameron AD, Brennand J (2011) Short-term outcomes following intrauterine transfusion in Scotland. Arch Dis Child Fetal Neonatal Ed 96(1):F69–F70

    Article  Google Scholar 

  34. Weisz B, Rosenbaum O, Chayen B, Peltz R, Feldman B, Lipitz S (2009) Outcome of severely anaemic fetuses treated by intrauterine transfusions. Arch Dis Child Fetal Neonatal Ed 94(3):F201–F204

    Article  CAS  Google Scholar 

  35. Meyer MP, Mildenhall L (2012) Delayed cord clamping and blood flow in the superior vena cava in preterm infants: an observational study. Arch Dis Child Fetal Neonatal Ed 97(6):F484–F486

    Article  Google Scholar 

  36. Sommers R, Stonestreet BS, Oh W, Laptook A, Yanowitz TD, Raker C, Mercer J (2012) Hemodynamic effects of delayed cord clamping in premature infants. Pediatrics. 129(3):e667–e672

    Article  Google Scholar 

  37. Baenziger O, Stolkin F, Keel M, von Siebenthal K, Fauchere J-C, Das Kundu S, Dietz V, Bucher HU, Wolf M (2007) The influence of the timing of cord clamping on postnatal cerebral oxygenation in preterm neonates: a randomized, controlled trial. Pediatrics. 119(3):455–459

    Article  Google Scholar 

  38. Popat H, Robledo KP, Sebastian L, Evans N, Gill A, Kluckow M, Sinhal S, Waal K, Tarnow-Mordi W, Osborn D (2018) Interobserver agreement and image quality of functional cardiac ultrasound measures used in a randomised trial of delayed cord clamping in preterm infants. Arch Dis Child Fetal Neonatal Ed 103(3):F257–F263

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, Division of Neonatology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

    Tanushree Sahoo, Anu Thukral, M Jeeva Sankar, Ramesh Agarwal, Ashok K Deorari & Vinod K Paul

  2. Department of Cardiology, Division of Pediatric Cardiology, All India Institute of Medical Sciences, New Delhi, India

    Saurabh Kumar Gupta

Authors
  1. Tanushree Sahoo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anu Thukral
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Jeeva Sankar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saurabh Kumar Gupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ramesh Agarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ashok K Deorari
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Vinod K Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Tanushree Sahoo conceptualised and designed the study, developed the protocol, recruited patients, performed echocardiography, collected data, and prepared the first draft.

Dr. Anu Thukral conceptualised and designed the study, coordinated and supervised data collection, critically reviewed the manuscript, and approved the final version of the manuscript.

Dr. M Jeeva Sankar helped in protocol development and statistical analysis of results and reviewed and revised the manuscript. Dr. Ramesh Agarwal helped in protocol development, reviewed and revised the manuscript.

Dr. Saurabh Kumar Gupta helped in protocol development, supervised and did quality check of bedside screening echocardiography, and reviewed the manuscript.

Dr. Ashok K Deorari helped in protocol development and critically reviewed the manuscript for important intellectual content.

Dr. Vinod K Paul helped in protocol development and critically reviewed the manuscript for improving the content.All the authors approved the final manuscript as submitted and agree to be accountable for all aspect of the work.

Corresponding author

Correspondence to Anu Thukral.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Institute Ethics Committee on 14 December 2016, ref no. IECPG-545/26.10.2016, RT-11/08.12.2016.

Informed consent

Informed consent was obtained from legally accepted representatives of all neonates included in the study.

Additional information

Communicated by Patrick Van Reempts

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(DOCX 59 kb)

ESM 2

(DOCX 23 kb)

ESM 3

(DOCX 51 kb)

ESM 4

(PDF 59 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sahoo, T., Thukral, A., Sankar, M.J. et al. Delayed cord clamping in Rh-alloimmunised infants: a randomised controlled trial. Eur J Pediatr 179, 881–889 (2020). https://doi.org/10.1007/s00431-020-03578-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-020-03578-8

Keywords

Search

Navigation