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Effect of delayed cord clamping on stem cell transfusion and hematological parameters in preterm infants with placental insufficiency: a pilot randomized trial

Abstract

The feasibility of delayed cord clamping (DCC) in preterm infants with placental insufficiency (PI) is questionable. We aimed to study the effect of DCC on stem cell transfusion, hematological parameters, and clinical outcomes in preterm infants born to mothers with PI. Preterm infants, < 34 weeks’ gestation, born to mothers with PI were randomized based on the timing of umbilical cord clamping into delayed clamping for 60 s (DCC group) or immediate cord clamping (ICC group) groups at time of birth. CD34 percentage as a marker of stem cell transfusion, early and late-onset anemia, hypothermia, hypotension, polycythemia, hyperbilirubinemia, duration of oxygen therapy, bronchopulmonary dysplasia, intra-ventricular hemorrhage, necrotizing enterocolitis, sepsis, mortality, and length of hospital stay were compared between studied groups. We found that peripheral blood CD34 percentage was significantly higher in DCC compared with that in the ICC group (median (IQR) of 0.5 (0.40–0.7) versus 0.35 (0.20–0.5), p = 0.004). Infants in the DCC group had significantly lower episodes of anemia of prematurity at 2 months, red blood cell transfusion, and shorter duration of oxygen therapy compared with those in the ICC group.

Conclusion: In conclusion, DCC compared with ICC increased stem cell transfusion and decreased early- and late-onset anemia in preterm infants with placental insufficiency.

Trial registration: NCT03731546 www.clinicaltrials.gov

What is Known:
• Delayed cord clamping has been recommended by the American Academy of Pediatrics as a standard of care practice during delivery of preterm infants.
• The feasibility of DCC in preterm infants with placental insufficiency (PI) is uncertain.
What is New:
• This randomized controlled trial demonstrated that DCC in the delivery room care of preterm infants born to mothers with placental insufficiency increased stem cell transfusion and decreased early- and late-onset anemia.

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Abbreviations

BPD:

Bronchopulmonary dysplasia

CPAP:

Continuous positive airway pressure

DCC:

Delayed cord clamping

DCC+NP:

Delayed cord clamping and normal placenta

DCC+PI:

Delayed cord clamping and placental insufficiency

ICC:

Immediate cord clamping

ICC+PI:

Immediate cord clamping and placental insufficiency

ELBW:

Extreme low birth weight infant

IUGR:

Intrauterine growth retardation

NEC:

Necrotizing enterocolitis

NICU:

Neonatal intensive care unit

SGA:

Small for gestational age

References

  1. Abule RM, Bernardes LS, Doro GF, Miyadahira S, Francisco RP (2016) Reduced placental volume and flow in severe growth restricted fetuses. Clinics (Sao Paulo) 71:332–337

    Article  Google Scholar 

  2. Aladangady N, McHugh S, Aitchison TC, Wardrop CA, Holland BM (2006) Infants’ blood volume in a controlled trial of placental transfusion at preterm delivery. Pediatrics 117:93–98

    Article  Google Scholar 

  3. Allan DS, Scrivens N, Lawless T, Mostert K, Oppenheimer L, Walker M, Petraszko T, Elmoazzen H (2016) Delayed clamping of the umbilical cord after delivery and implications for public cord blood banking. Transfusion 56:662–665

    Article  Google Scholar 

  4. Backes CH, Rivera BK, Haque U, Bridge JA, Smith CV, Hutchon DJ, Mercer JS (2014) Placental transfusion strategies in very preterm neonates: a systematic review and meta-analysis. Obstet Gynecol 124:47–56

    Article  Google Scholar 

  5. (2017) Delayed umbilical cord clamping after birth. Pediatrics 139(6):e20170957. https://doi.org/10.1542/peds.2017-0957

  6. Farrar D, Airey R, Law GR, Tuffnell D, Cattle B, Duley L (2011) Measuring placental transfusion for term births: weighing babies with cord intact. BJOG 118:70–75

    CAS  Article  Google Scholar 

  7. 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 218:1–18

    Article  Google Scholar 

  8. Gokmen Z, Ozkiraz S, Tarcan A, Kozanoglu I, Ozcimen EE, Ozbek N (2011) Effects of delayed umbilical cord clamping on peripheral blood hematopoietic stem cells in premature neonates. J Perinat Med 39:323–329

    Article  Google Scholar 

  9. Haneline LS, Marshall KP, Clapp DW (1996) The highest concentration of primitive hematopoietic progenitor cells in cord blood is found in extremely premature infants. Pediatr Res 39:820–825

    CAS  Article  Google Scholar 

  10. Harrington K, Carpenter RG, Nguyen M, Campbell S (1995) Changes observed in Doppler studies of the fetal circulation in pregnancies complicated by pre-eclampsia or the delivery of a small-for-gestational-age baby. I. Cross-sectional analysis. Ultrasound Obstet Gynecol 6:19–28

    CAS  Article  Google Scholar 

  11. Jobe AH, Bancalari E (2001) Bronchopulmonary dysplasia. Am J Respir Crit Care Med 163:1723–1729

    CAS  Article  Google Scholar 

  12. Kaempf JW, Tomlinson MW, Kaempf AJ, Wu Y, Wang L, Tipping N, Grunkemeier G (2012) Delayed umbilical cord clamping in premature neonates. Obstet Gynecol 120:325–330

    Article  Google Scholar 

  13. Kc A, Rana N, Malqvist 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 171:264–270

    Article  Google Scholar 

  14. Lawton C, Acosta S, Watson N, Gonzales-Portillo C, Diamandis T, Tajiri N, Kaneko Y, Sanberg PR, Borlongan CV (2015) Enhancing endogenous stem cells in the newborn via delayed umbilical cord clamping. Neural Regen Res 10:1359–1362

    Article  Google Scholar 

  15. Mercer J, Erickson-Owens D (2006) Delayed cord clamping increases infants’ iron stores. Lancet 367:1956–1958

    Article  Google Scholar 

  16. Mercer JS, Erickson-Owens DA, Collins J, Barcelos MO, Parker AB, Padbury JF (2016) Effects of delayed cord clamping on residual placental blood volume, hemoglobin and bilirubin levels in term infants: a randomized controlled trial. J Perinatol 37:260–264

    Article  Google Scholar 

  17. Mercer JS, Vohr BR, McGrath MM, Padbury JF, Wallach M, Oh W (2006) Delayed cord clamping in very preterm infants reduces the incidence of intraventricular hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 117:1235–1242

    Article  Google Scholar 

  18. Committee on Obstetric Practice (2017) Committee opinion no. 684: delayed umbilical cord clamping after birth. Obstet Gynecol 129(1):e5–e10. https://doi.org/10.1097/AOG.0000000000001860

    Article  Google Scholar 

  19. 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(9):CD003248

    PubMed  Google Scholar 

  20. Snijders RJ, De Courcy-Wheeler RH, Nicolaides KH (1994) Intrauterine growth retardation and fetal transverse cerebellar diameter. Prenat Diagn 14:1101–1105

    CAS  Article  Google Scholar 

  21. 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 (2017) Delayed versus immediate cord clamping in preterm infants. N Engl J Med 377:2445–2455

    Article  Google Scholar 

  22. Ultee CA, van der Deure J, Swart J, Lasham C, van Baar AL (2008) Delayed cord clamping in preterm infants delivered at 34 36 weeks’ gestation: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 93:F20–F23

    CAS  Article  Google Scholar 

  23. Walsh MC, Kliegman RM (1986) Necrotizing enterocolitis: treatment based on staging criteria. Pediatr Clin N Am 33:179–201

    CAS  Article  Google Scholar 

  24. 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 

  25. Wyckoff MH, Aziz K, Escobedo MB, Kapadia VS, Kattwinkel J, Perlman JM, Simon WM, Weiner GM, Zaichkin JG (2015) Part 13: neonatal resuscitation: 2015 American Heart Association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation 132:S543–S560

    Article  Google Scholar 

  26. Yang S, Duffy JY, Johnston R, Fall C, Fitzmaurice LE (2019) Association of a delayed cord-clamping protocol with hyperbilirubinemia in term neonates. Obstet Gynecol 133:754–761

    Article  Google Scholar 

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Acknowledgments

We would like to thank Miss Eitemad Arafaa for her effort in randomization and allocation of infants into study groups. We would like to thank the parents and families in the Neonatal Intensive Care Unit at Mansoura University Children’s Hospital.

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Authors and Affiliations

Authors

Contributions

Mohammed Yunis participated in design of the study, data collection and writing the first draft of the manuscript. Nehad Nasef and Islam Nour participated in formulating the hypothesis, design of the study, data collection, data interpretation, statistical analysis, and writing of the manuscript. Basma Shouman and Mohamed Sarhan participated in design of the study, data collection, and writing of the manuscript. Ahmed Gibreel participated in design of the study, supervising the delayed cord clamping practice, obstetric data collection, data interpretation and writing the manuscript. Mohamad Darwish participated in laboratory analysis, data interpretation, and writing of the manuscript. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Nehad Nasef.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

This article has been approved by the local Medical Research Ethics Committee of Faculty of Medicine, University of Mansoura, Egypt.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Communicated by Daniele De Luca

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Yunis, M., Nour, I., Gibreel, A. et al. Effect of delayed cord clamping on stem cell transfusion and hematological parameters in preterm infants with placental insufficiency: a pilot randomized trial. Eur J Pediatr 180, 157–166 (2021). https://doi.org/10.1007/s00431-020-03730-4

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  • DOI: https://doi.org/10.1007/s00431-020-03730-4

Keywords

  • Preterm infant
  • Placental insufficiency
  • Stem cell
  • Umbilical cord
  • Anemia neonatorum