Timing of Umbilical Cord Clamping and Impact on Cord Blood Volume Collected for Banking

Timing of the umbilical cord clamping and the impact of placental transfusion for newborn health have been recently revisited and revised in numerous papers and a comprehensive meta-analysis¹. In this article we describe the impact of delayed cord clamping on cord blood collection.

In its most recent Committee Opinion, the American College of Obstetrics and Gynecology (AGOG²) states that there is evidence indicating that delayed cord clamping in preterm infants reduces intraventricular hemorrhage by nearly 50%. There might be additional benefits from the transfer of immunoglobulins and stem cells which have the potential to enhance organ repair necessary in situations caused by trauma and injuries resulting from pre-term birth. 

ACOG went on to summarize that for term babies, delayed cord clamping might result in increased blood volume, which has both potential advantages and disadvantages. The advantages might be a reduced need for blood transfusions and decreased frequency of iron anemia. The disadvantage is a higher frequency of jaundice with resulting increased need for phototherapy. Additionally, with delayed cord clamping there is a higher risk for maternal hemorrhage. Therefore, ACOG concludes that for term babies born in developed countries more studies are needed to confirm or refute the benefits of delayed cord clamping.

The Royal College of Obstetricians and Gynecologists (RCOG³) issued an opinion similar to ACOG. They agree that there is a need to review and reassess large randomized trials regarding the timing and benefits of delayed cord blood clamping.

We designed a study to explore the relationship between delayed (also known as deferred) cord blood clamping and the success of umbilical cord blood collection for public banking. The purpose of our study was not to evaluate whether delayed cord clamping is necessary, but to underline its impact on the collection of cord blood units (CBU) with high Total Nucleated Cell (TNC) counts. Since RCOG³ estimates that delayed cord clamping might result in the newborn receiving an additional placental transfusion of as much as 60-120mL of blood, it is of concern to ask how much blood remains to be collected from the umbilical cord.

To eliminate variance in practices among different hospitals, we followed a cohort of 552 women who agreed to cord blood donation, in one of the National Cord Blood Program (NCBP) collection sites. Of the 552 patients who consented to donating their infant’s cord blood, 373 delivered vaginally, and 179 delivered via cesarean section (similar percentages are in all collection sites). The cord blood collections were performed ex utero by trained staff of NCBP bank after obtaining bi-institutional IRB approved Informed Consent.

In order to qualify for processing, cryopreservation, testing and retention in the inventory for future allogeneic transplantation, our public bank requires that collected cord blood units meet or exceed a high TNC threshold of 1.60 x10⁹ (1.6 billion TNC) as assessed by NCBP staff at the hospital collection site (with a hematology analyzer).

From the 552 collected CBU, 78 cord blood units were above the 1.6 billion TNC threshold, a cumulative success rate of 14% for this high TNC cut-off. In our study we defined immediate clamping (or non- delayed) as occurring from 5-60 seconds, and delayed clamping was considered to be above 60 seconds. The delayed clamping cohort was further divided in two sub-groups: 60-120 seconds, and above 120 seconds.

Delayed clamping occurred in 125 cases (22.6% of total deliveries) in our study, of which only 3 collections (all 3 of them from vaginal deliveries) reached the TNC threshold for a clinical CBU, a 2.4% success rate. By comparison, 427 deliveries which did not have delayed clamping resulted in 75 clinical-grade CBU. The success rate for collecting clinical grade cord blood units is 17.6% with cord clamping time less than 60 seconds. This is 7.3 times higher than in delayed clamping deliveries. The delayed clamping was performed in 5 cesarean sections, and in 120 vaginal deliveries, numbers in concordance with previously reported data.

In the table below we summarize the mean TNC counts for each of studied cohorts. There is a statistically significant decrease of TNC values with increased clamping delay: The difference in mean TNC between a clamping delay below 60 seconds versus all the clamping times above 60 seconds had p<0.001, and the difference in mean TNC between a delay of 60-120 seconds versus above 120 seconds had p<0.05.

Since the biggest hurdle encountered when using cord blood grafts for allogeneic stem cell transplants is their total nucleated cell dose, the collection of CBU with high TNC is imperative. However, our study indicates that the chances of obtaining a high TNC cord blood unit (at least 1.6 billion TNC) are 2.4% in the delayed clamping cohort and 17.6% in the non-delayed clamping cohort. The success rate of cord blood donation is more than 7 times higher when the cord clamping delay is less than a minute.

These numbers are significant not only for cord blood donation for the public but also for private cord blood storage for family use. We believe that parents should be properly informed about the real benefits and risks of delayed cord blood clamping in relationship with either public or private cord blood banking in developed nations.

Rodica Ciubotariu, MD PhD received her Medical Degree from University of Medicine, Bucharest, Romania and her PhD from Columbia University. Before joining the National Cord Blood Program of the NY Blood Center as Director of Donor Services, her research focus was aimed at immunology of graft rejection and the discovery of a new subset of immunoregulatory T cells. She has published more than 20 articles in peer-reviewed journals, and currently she also serves as a FACT inspector and co-chair of the FACT Collections Committee.

References

1. The Cochrane Collaboration, 2014. Effect of Timing of Umbilical Cord Clamping of Term Infants on Maternal and Neonatal Outcomes
2. The American College of Obstetricians and Gynecologists (ACOG) Committee Opinion- Timing of Umbilical Cord Blood Clamping After Birth, number 543, Reaffirmed 2014
3. Royal College of Obstetricians and Gynaecologists (RCOG) - Clamping of the Umbilical Cord and Placental Transfusion, Scientific Impact Paper No.14, February 2015
4. Ciubotariu R, Lloyd S, Ciubotariu I, et al. Timing of umbilical cord blood clamping and its impact on cord blood banking. Transfusion 2016; 56:1A-12A.
5. Ciubotariu R, Scaradavou A, Ciubotariu I, Tarnawski M, Lloyd S, Albano M, Dobrila L, Rubinstein P, Grunebaum A. Impact of delayed umbilical cord clamping on public cord blood donations: can we help future patients and benefit infant donors? Transfusion 2018; 58:1427-1433.