Abstract
Background
Neonatal Resuscitation Program does not recommend placental transfusion in depressed preterm neonates.
Methods
Our objectives were to study the effect of delayed cord clamping (DCC) with ventilation for 5 min (DCCV, n-5), umbilical cord milking (UCM) without ventilation (n-6), UCM with ventilation (UCMV, n-6), early cord clamping followed by ventilation (ECCV, n-6) on red cell volume (RCV), and hemodynamic changes in asphyxiated preterm lambs. Twenty-three preterm lambs at 127–128 days gestation were randomized to DCCV, UCM, UCMV, and ECCV. We defined asphyxia as heart rate <100/min.
Results
The UCMV had the highest neonatal RCV as a percentage of fetoplacental volume compared to the other groups (UCMV 85.5 ± 10%, UCM 72 ± 10%, ECCV 65 ± 14%, DCCV 61 ± 10%, p < 0.01). The DCCV led to better ventilation (66 ± 1 mmHg) and higher pulmonary blood flow (75 ± 24 ml/kg/min). The carotid flow was significantly higher in UCM without ventilation. The fluctuations in carotid flow with milking were 25 ± 6% higher from baseline during UCM, compared to 6 ± 3% in UCMV (p < 0.01).
Conclusions
Cord milking with ventilation led to higher RCV than other interventions. Ventilation during cord milking reduced fluctuation in carotid flow compared to UCM alone. DCCV led to better ventilation and pulmonary blood flow but did not increase RCV.
Impact
-
The best practice of placental transfusion in a depressed preterm neonate remains unknown.
-
Ventilation with an intact cord improves gas exchange and hemodynamics in an asphyxiated preterm model.
-
Cord milking without ventilation led to lower red cell volume but higher carotid blood flow fluctuations compared to milking with ventilation.
-
Our data can be translated to bedside and could impact preterm resuscitation.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 13 print issues and online access
$259.00 per year
only $19.92 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout






Data availability
Data presented in this manuscript will be available after complete analysis (2-hour data) is done on request.
References
Perlman, J. M. et al. Part 7: Neonatal Resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Circulation 132(Suppl 1), S204–S241 (2015).
Rabe, H., Diaz-Rossello, J. L., 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 Syst. Rev. 8, CD003248 (2012).
Rabe, H., Reynolds, G. & Diaz-Rossello, J. Early versus delayed umbilical cord clamping in preterm infants. Cochrane Database Syst. Rev. 4, CD003248 (2004).
Tarnow-Mordi, W. et al. Delayed versus immediate cord clamping in preterm infants. N. Engl. J. Med. 377, 2445–2455 (2017).
Katheria, A. C. Delayed cord clamping may not be beneficial in the premature infant. J. Pediatr. 196, 324–327 (2018).
Polglase, G. R. et al. Ventilation onset prior to umbilical cord clamping (physiological-based cord clamping) improves systemic and cerebral oxygenation in preterm lambs. PLoS ONE 10, e0117504 (2015).
Katheria, A. C. et al. Delayed cord clamping in newborns born at term at risk for resuscitation: a feasibility randomized clinical trial. J. Pediatr. 187, 313.e1–317.e1 (2017).
Katheria, A., Blank, D., Rich, W. & Finer, N. Umbilical cord milking improves transition in premature infants at birth. PLoS ONE 9, e94085 (2014).
Katheria, A. et al. A randomized clinical trial of umbilical cord milking vs delayed cord clamping in preterm infants: neurodevelopmental outcomes at 22-26 months of corrected age. J. Pediatr. 194, 76–80 (2018).
Blank, D. A. et al. Haemodynamic effects of umbilical cord milking in premature sheep during the neonatal transition. Arch. Dis. Child. Fetal Neonatal Ed. 103, F539–F546 (2018).
Chandrasekharan, P. et al. Effect of various inspired oxygen concentrations on pulmonary and systemic hemodynamics and oxygenation during resuscitation in a transitioning preterm model. Pediatr. Res. 84, 743–750 (2018).
Strauss, R. G. 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 43, 1168–1172 (2003).
Bhatt, S. et al. Delaying cord clamping until ventilation onset improves cardiovascular function at birth in preterm lambs. J. Physiol. 591(Pt. 8), 2113–2126 (2013).
Weiner, G. M. & Zaichkin, J. (eds) Textbook of Neonatal Resuscitation (NRP) 7th edn (American Academy of Pediatrics, 2016).
Lakshminrusimha, S. & Jobe, A. H. Baby’s first cries and establishment of gas exchange in the lung. Am. J. Respir. Crit. Care Med. 204, 11–13 (2021).
Tingay, D. G. et al. Imaging the respiratory transition at birth: unravelling the complexities of the first breaths of life. Am. J. Respir. Crit. Care Med. 204, 82–91 (2021).
Oei, J. L. et al. Outcomes of oxygen saturation targeting during delivery room stabilisation of preterm infants. Arch. Dis. Child. Fetal Neonatal Ed. 103, F446–F454 (2017).
Kapadia, V. et al. Outcomes of delivery room resuscitation of bradycardic preterm infants: a retrospective cohort study of randomised trials of high vs low initial oxygen concentration and an individual patient data analysis. Resuscitation 167, 209–217 (2021).
March, M. I., Hacker, M. R., Parson, A. W., Modest, A. M. & de Veciana, M. The effects of umbilical cord milking in extremely preterm infants: a randomized controlled trial. J. Perinatol. 33, 763–767 (2013).
Katheria, A. C., Truong, G., Cousins, L., Oshiro, B. & Finer, N. N. Umbilical cord milking versus delayed cord clamping in preterm infants. Pediatrics 136, 61–69 (2015).
Andersson, O. et al. Intact cord resuscitation versus early cord clamping in the treatment of depressed newborn infants during the first 10 min of birth (Nepcord III) - a randomized clinical trial. Matern. Health Neonatol. Perinatol. 5, 15 (2019).
Chandrasekharan, P. et al. Resuscitation with an intact cord enhances pulmonary vasodilation and ventilation with reduction in systemic oxygen exposure and oxygen load in an asphyxiated preterm ovine model. Children 8, 307 (2021).
Lakshminrusimha, S., Vali, P., Chandrasekharan, P., Rich, W. & Katheria, A. Differential alveolar and systemic oxygenation during preterm resuscitation with 100% oxygen during delayed cord clamping. Am. J. Perinatol. https://doi.org/10.1055/s-0041-1730362 (2021).
Padilla-Sanchez, C. et al. Delayed vs immediate cord clamping changes oxygen saturation and heart rate patterns in the first minutes after birth. J. Pediatr. 227, 149.e1–156.e1 (2020).
Rudolph, A. M. & Heymann, M. A. Cardiac output in the fetal lamb: the effects of spontaneous and induced changes of heart rate on right and left ventricular output. Am. J. Obstet. Gynecol. 124, 183–192 (1976).
Yigit, B., Tutsak, E., Yildirim, C., Hutchon, D. & Pekkan, K. Transitional fetal hemodynamics and gas exchange in premature postpartum adaptation: immediate vs. delayed cord clamping. Matern. Health Neonatol. Perinatol. 5, 5 (2019).
Katheria, A. C., Brown, M. K., Rich, W. & Arnell, K. Providing a placental transfusion in newborns who need resuscitation. Front. Pediatr. 5, 1 (2017).
Chawla, S., Chock, V. Y. & Lakshminrusimha, S. Intraventricular hemorrhage and white matter injury: is persistent cerebral desaturation a missing link? Pediatr. Res. 89, 727–729 (2021).
Stenning, F. J. et al. Transfusion or timing: the role of blood volume in delayed cord clamping during the cardiovascular transition at birth. Front. Pediatr. 7, 405 (2019).
Katheria, A. et al. Association of umbilical cord milking vs delayed umbilical cord clamping with death or severe intraventricular hemorrhage among preterm infants. JAMA 322, 1877–1886 (2019).
Rabe, H. & Andersson, O. Maternal and infant outcomes after different methods of umbilical cord management. JAMA 322, 1864–1865 (2019).
Funding
This work was financially supported by R01HD104909, R03HD096510, K12 HL138052, AAP NRP grant, Zoll Foundation grant, and University at Buffalo—Dr. Henry C. and Bertha H. Buswell Grant to P.C.; R03HD104062 to M.R.; and R01HD072929 to S.L.
Author information
Authors and Affiliations
Contributions
P.C.—conceptualization, methodology, data acquisition and analysis, interpretation, writing—original draft, critically reviewing, and editing. S.G., C.K., J.H., L.N., N.B., J.N., D.S., M.B., M.R.—data acquisition, extraction, critical reviewing, and manuscript editing. S.L.—methodology, data interpretation, critically reviewing, editing, and provided illustration. All authors approved the final version for publication.
Corresponding author
Ethics declarations
Competing interests
S.L. is a neonatal resuscitation program steering committee member. All other authors report no conflicts of interest. The research reported here is not endorsed by the funding institutions or the neonatal resuscitation program.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Chandrasekharan, P., Gugino, S., Koenigsknecht, C. et al. Placental transfusion during neonatal resuscitation in an asphyxiated preterm model. Pediatr Res 92, 678–684 (2022). https://doi.org/10.1038/s41390-022-02086-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41390-022-02086-9
This article is cited by
-
From “A family of NICU graduates” to “A family of four”
Pediatric Research (2022)