Skip to main content
SpringerLink
Log in

Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial

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

Abstract

Recommendations for umbilical cord management in intrauterine growth-restricted (IUGR) neonates are lacking. The present randomized controlled trial compared hemodynamic effects of umbilical cord milking (UCM) with delayed cord clamping (DCC) in IUGR neonates > 28 weeks of gestation, not requiring resuscitation. One hundred seventy IUGR neonates were randomly allocated to intact UCM (4 times squeezing of 20 cm intact cord; n = 85) or DCC (cord clamping after 60 s; n = 85) immediately after delivery. The primary outcome variable was superior vena cava (SVC) blood flow at 24 ± 2 h. Secondary outcomes assessed were anterior cerebral artery (ACA) and superior mesenteric artery (SMA) blood flow indices, right ventricular output (RVO), regional cerebral oxygen saturation (CrSO2) and venous hematocrit at 24 ± 2 h, peak total serum bilirubin (TSB), incidences of in-hospital complications, need and duration of respiratory support, and hospital stay. SVC flow was significantly higher in UCM compared to DCC (111.95 ± 33.54 and 99.49 ± 31.96 mL/kg/min, in UCM and DCC groups, respectively; p < 0.05). RVO and ACA/SMA blood flow indices were comparable whereas CrSO2 was significantly higher in UCM group. Incidences of polycythemia and jaundice requiring phototherapy were similar despite significantly higher venous hematocrit and peak TSB in UCM group. The need for non-invasive respiratory support was significantly higher in UCM group though the need and duration of mechanical ventilation and other outcomes were comparable.

Conclusions: UCM significantly increases SVC flow, venous hematocrit, and CrSO2 compared to DCC in IUGR neonates without any difference in other hemodynamic parameters and incidences of polycythemia and jaundice requiring phototherapy; however, the need for non-invasive respiratory support was higher with UCM.

Trial registration: Clinical trial registry of India (CTRI/2021/03/031864).

What is Known:

• Umbilical cord milking (UCM) increases superior vena cava blood flow (SVC flow) and hematocrit without increasing the risk of symptomatic polycythemia and jaundice requiring phototherapy in preterm neonates compared to delayed cord clamping (DCC).

• An association between UCM and intraventricular hemorrhage in preterm neonates < 28 weeks of gestation is still being investigated.

What is New:

• Placental transfusion by UCM compared to DCC increases SVC flow, regional cerebral oxygenation, and hematocrit without increasing the incidence of symptomatic polycythemia and jaundice requiring phototherapy in intrauterine growth-restricted neonates.

• UCM also increases the need for non-invasive respiratory support compared to DCC.

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

Similar content being viewed by others

Availability of data and material

Deidentified individual participant data (including data dictionaries) will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. Proposals should be submitted to chaitra.s.angadi@gmail.com.

Code availability

N/A.

Abbreviations

ACA:

Anterior cerebral artery

CBF:

Cerebral blood flow

CI:

Confidence interval

CPAP:

Continuous positive airway pressure

CrSO2 :

Regional cerebral oxygenation saturation

CTRI:

Clinical Trial Registry of India

DCC:

Delayed cord clamping

DR-CPAP:

Delivery room continuous positive airway pressure

ECC:

Early cord clamping

EDV:

End-diastolic velocity

GA:

Gestational age

IQR:

Interquartile range

IUGR:

Intrauterine growth restriction

IVH:

Intraventricular hemorrhage

MD:

Mean difference

n :

Number

N :

Total number in that population

NEC:

Necrotizing enterocolitis

PSV:

Peak systolic velocity

RCT:

Randomized controlled trial

RI:

Resistive index

RR:

Relative risk

RVO:

Right ventricular output

SD:

Standard deviation

SMA:

Superior mesenteric artery

SVC:

Superior vena cava

TSB:

Total serum bilirubin

UA:

Umbilical artery

VTI:

Velocity time integral

References

  1. Aziz K, Lee CHC, Escobedo MB, Hoover AV, Kamath-Rayne BD, Kapadia VS, Magid DJ, Niermeyer S, Schmölzer GM, Szyld E et al (2021) Part 5: Neonatal Resuscitation 2020 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Pediatrics 147(Suppl 1):e2020038505E

    Article  PubMed  Google Scholar 

  2. Madar J, Roehr CC, Ainsworth S, Ersdal H, Morley C, Rüdiger M, Skåre C, Szczapa T, Te Pas A, Trevisanuto D et al (2021) European Resuscitation Council Guidelines 2021: newborn resuscitation and support of transition of infants at birth. Resuscitation 161:291–326

    Article  PubMed  Google Scholar 

  3. Rabe H, Gyte GM, Díaz-Rossello JL, Duley L (2019) 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 9:CD003248

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

    Article  PubMed  Google Scholar 

  5. Chopra A, Thakur A, Garg P, Kler N, Gujral K (2018) Early versus delayed cord clamping in small for gestational age infants and iron stores at 3 months of age - a randomized controlled trial. BMC Pediatr 18:234

    Article  PubMed  PubMed Central  Google Scholar 

  6. Digal KC, Singh P, Srivastava Y, Chaturvedi J, Tyagi AK, Basu S (2021) Effects of delayed cord clamping in intrauterine growth-restricted neonates: a randomized controlled trial. Eur J Pediatr 180:1701–1710

    Article  PubMed  Google Scholar 

  7. Brown BE, Shah PS, Afifi JK, Sherlock RL, Adie MA, Monterrosa LA, Crane JM, Ye XY, El-Naggar WI, Neonatal C, Network; Canadian Preterm Birth Network Investigators, (2022) Delayed cord clamping in small for gestational age preterm infants. Am J Obstet Gynecol 226:247.e1-247.e10

    Article  PubMed  Google Scholar 

  8. Katheria AC, Truong G, Cousins L, Oshiro B, Finer NN (2015) Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 136:61–69

    Article  PubMed  PubMed Central  Google Scholar 

  9. Mangla MK, Thukral A, Sankar MJ, Agarwal R, Deorari AK, Paul VK (2020) Effect of umbilical cord milking vs delayed cord clamping on venous hematocrit at 48 hours in late preterm and term neonates: a randomized controlled trial. Indian Pediatr 57:1119–1123

    Article  PubMed  Google Scholar 

  10. Jaiswal P, Upadhyay A, Gothwal S, Singh D, Dubey K, Garg A, Vishnubhatala S (2015) Comparison of two types of intervention to enhance placental redistribution in term infants: randomized control trial. Eur J Pediatr 174:1159–1167

    Article  PubMed  Google Scholar 

  11. Sura M, Osoti A, Gachuno O, Musoke R, Kagema F, Gwako G, Ondieki D, Ndavi PM, Ogutu O (2021) Effect of umbilical cord milking versus delayed cord clamping on preterm neonates in Kenya: a randomized controlled trial. PLoS ONE 16:e0246109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Katheria A, Reister F, Essers J, Mendler M, Hummler H, Subramaniam A, Carlo W, Tita A, Truong G, Davis-Nelson S et al (2019) Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 322:1877–1886

    Article  PubMed  PubMed Central  Google Scholar 

  13. Katheria AC, Szychowski JM, Essers J, Mendler MR, Dempsey EM, Schmölzer GM, Arnell K, Rich WD, Hassen K, Allman P et al (2020) Early cardiac and cerebral hemodynamics with umbilical cord milking compared with delayed cord clamping in infants born preterm. J Pediatr 223:51-56.e1

    Article  PubMed  PubMed Central  Google Scholar 

  14. Montaldo P, Puzone S, Caredda E, Pugliese U, Inserra E, Cirillo G, Gicchino F, Campana G, Ursi D, Galdo F et al (2022) Impact of intrauterine growth restriction on cerebral and renal oxygenation and perfusion during the first 3 days after birth. Sci Rep 12:5067

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Papageorghiou AT, Ohuma EO, Altman DG, Todros T, Cheikh Ismail L, Lambert A, Jaffer YA, Bertino E, Gravett MG, Purwar M, International Fetal and Newborn Growth Consortium for the 21st Century (INTERGROWTH-21st) et al (2014) International standards for fetal growth based on serial ultrasound measurements: the Fetal Growth Longitudinal Study of the INTERGROWTH-21st Project. Lancet 384:869–879

  16. Papile LA, Burstein J, Burstein R, Koffler H (1978) Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm. J Pediatr 92:529–534

    Article  CAS  PubMed  Google Scholar 

  17. Fanaro S (2013) Feeding intolerance in the preterm infant. Early Hum Dev 89(Suppl 2):S13-20

    Article  PubMed  Google Scholar 

  18. Kliegman RM, Walsh MC (1987) Neonatal necrotizing enterocolitis: pathogenesis, classification, and spectrum of illness. Curr Probl Pediatr 17:213–288. https://doi.org/10.1016/0045-9380(87)90031-4

    Article  CAS  PubMed  Google Scholar 

  19. Evans N, Kluckow M, Simmons M, Osborn D (2002) Which to measure, systemic or organ blood flow? Middle cerebral artery and superior vena cava flow in very preterm infants. Arch Dis Child Fetal Neonatal Ed 87:F181–F184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yanowitz TD, Yao AC, Pettigrew KD, Werner JC, Oh W (1985) Stonestreet BS (1999) Postnatal hemodynamic changes in very-low-birth weight infants. J Appl Physiol 87:370–380

    Article  Google Scholar 

  21. Kluckow M, Evans N (2000) Superior vena cava flow in newborn infants: a novel marker of systemic blood flow. Arch Dis Child Fetal Neonatal Ed 82:F182–F187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. American Academy of Pediatrics Subcommittee on Hyperbilirubinemia (2004) Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 114:297–316. https://doi.org/10.1542/peds.114.1.297.Erratum.In:Pediatrics114:1138

    Article  Google Scholar 

  23. National Collaborating Centre for Women’s and Children’s Health. Neonatal jaundice: Clinical guideline. 2010. https://www.nice.org.uk/guidance/cg98/evidence/full-guideline-245411821.  Last accessed on 13 March, 2023

  24. Turan OM, Turan S, Gungor S, Berg C, Moyano D, Gembruch U, Nicolaides KH, Harman CR, Baschat AA (2008) Progression of Doppler abnormalities in intrauterine growth restriction. Ultrasound Obstet Gynecol 32:160–167

    Article  CAS  PubMed  Google Scholar 

  25. Leipälä JA, Boldt T, Turpeinen U, Vuolteenaho O, Fellman V (2003) Cardiac hypertrophy and altered hemodynamic adaptation in growth-restricted preterm infants. Pediatr Res 53:989–993

    Article  PubMed  Google Scholar 

  26. Sehgal A, Doctor T, Menahem S (2013) Cardiac function and arterial biophysical properties in small for gestational age infants: postnatal manifestations of fetal programming. J Pediatr 63:1296–1300

    Article  Google Scholar 

  27. Drayton MR, Skidmore R (1987) Vasoactivity of the major intracranial arteries in newborn infants. Arch Dis Child 62:236–240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Sloot SC, de Waal KA, van der Lee JH, van Kaam AH (2010) Central blood flow measurements in stable preterm infants after the transitional period. Arch Dis Child Fetal Neonatal Ed 95:F369–F372

    Article  CAS  PubMed  Google Scholar 

  29. Giussani DA (2016) The fetal brain sparing response to hypoxia: physiological mechanisms. J Physiol 594:1215–1230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cohen E, Baerts W, van Bel F (2015) Brain-sparing in intrauterine growth restriction: considerations for the neonatologist. Neonatology 108:269–276

    Article  PubMed  Google Scholar 

  31. Banait N, Suryawanshi P, Malshe N, Nagpal R, Lalwani S (2013) Cardiac blood flow measurements in stable full term small for gestational age neonates. J Clin Diagn Res 7:1651–1654

    PubMed  PubMed Central  Google Scholar 

  32. Farag MM, Thabet MAEH, Abd-Almohsen AM, Ibrahim HIAM (2022) The effect of placental transfusion on hemodynamics in premature newborns: a randomized controlled trial. Eur J Pediatr 181:4121–4133

    Article  PubMed  PubMed Central  Google Scholar 

  33. Finn D, Ryan DH, Pavel A, O’Toole JM, Livingstone V, Boylan GB, Kenny LC, Dempsey EM (2019) Clamping the Umbilical Cord in Premature Deliveries (CUPiD): neuromonitoring in the immediate newborn period in a randomized, controlled trial of preterm infants born at <32 weeks of gestation. J Pediatr 208:121-126.e2

    Article  PubMed  Google Scholar 

  34. Rabe H, Jewison A, Fernandez Alvarez R, Crook D, Stilton D, Bradley R, Holden D; Brighton Perinatal Study Group (2011) Milking compared with delayed cord clamping to increase placental transfusion in preterm neonates: a randomized controlled trial. Obstet Gynecol 117(2 Pt 1):205–211

    Google Scholar 

  35. Shirk SK, Manolis SA, Lambers DS, Smith KL (2019) Delayed clamping vs milking of umbilical cord in preterm infants: a randomized controlled trial. Am J Obstet Gynecol 220:482.e1-482.e8

    Article  PubMed  Google Scholar 

  36. Hosono S, Mugishima H, Fujita H, Hosono A, Minato M, Okada T, Takahashi S, Harada K (2008) 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 93:F14–F19

    Article  CAS  PubMed  Google Scholar 

  37. Ortiz-Esquinas I, Gómez-Salgado J, Rodriguez-Almagro J, Arias-Arias Á, Ballesta-Castillejos A, Hernández-Martínez A (2020) Umbilical cord milking in infants born at <37 weeks of gestation: a systematic review and meta-analysis. J Clin Med 9:1071

    Article  PubMed  PubMed Central  Google Scholar 

  38. Usher R, Shephard M, Lind J (1963) The blood volume of the newborn infant and placental transfusion. Acta Paediatr (Stockh) 52:497–512

    Article  CAS  PubMed  Google Scholar 

  39. Kumbhat N, Eggleston B, Davis AS, DeMauro SB, Van Meurs KP, Foglia EE, Lakshminrusimha S, Walsh MC, Watterberg KL, Wyckoff MH; Generic Database Subcommittee of the National Institute of Child Health and Human Development Neonatal Research Network et al (2021) Umbilical cord milking vs delayed cord clamping and associations with in-hospital outcomes among extremely premature infants. J Pediatr 232:87–94.e4

  40. Balasubramanian H, Ananthan A, Jain V, Rao SC, Kabra N (2020) Umbilical cord milking in preterm infants: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed 105:572–580

    Article  PubMed  Google Scholar 

  41. Blank DA, Polglase GR, Kluckow M, Gill AW, Crossley KJ, Moxham A, Rodgers K, Zahra V, Inocencio I, Stenning F et al (2018) Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition. Arch Dis Child Fetal Neonatal Ed 103:F539-546

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to thank all the study participants and their families who consented to join this study.

Author information

Authors and Affiliations

  1. Department of Neonatology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, 249203, India

    Chaitra Angadi, Poonam Singh, Mayank Priyadarshi, Suman Chaurasia & Sriparna Basu

  2. Department of Pediatrics, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

    Yash Shrivastava

  3. Department of Obstetrics & Gynecology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

    Jaya Chaturvedi

Authors
  1. Chaitra Angadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Poonam Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yash Shrivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mayank Priyadarshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Suman Chaurasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jaya Chaturvedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Sriparna Basu
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Dr. Chaitra recruited patients, collected and analyzed the data, and drafted the initial manuscript; Drs. Singh and Basu supervised data collection and analysis of the data and did critical revision and finalization of the manuscript; Dr. Shrivastava contributed to the study design, echocardiography, data analysis, and interpretation; Drs. Priyadarshi, Chaurasia, and Chaturvedi contributed to the study design, data analysis, and interpretation; and all authors approved the final manuscript as submitted.

Corresponding author

Correspondence to Poonam Singh.

Ethics declarations

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. The study protocol was approved by the Institute’s Ethics Committee of AIIMS Rishikesh, Uttarakhand, India (Ref No. AIIMS/IEC/21/103/dated 12/02/2021).

Consent to participate

Written informed consent was obtained from the parent of each subject before enrolment.

Consent for publication

Written informed consent was obtained from all the parents of the study participants for the publication of their data.

Conflict of interest

The authors declare no competing interests.

Additional information

Communicated by Daniele De Luca

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 14 KB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Angadi, C., Singh, P., Shrivastava, Y. et al. Effects of umbilical cord milking versus delayed cord clamping on systemic blood flow in intrauterine growth-restricted neonates: A randomized controlled trial. Eur J Pediatr 182, 4185–4194 (2023). https://doi.org/10.1007/s00431-023-05105-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-023-05105-x

Keywords

Search

Navigation