Circadian and circannual variations in cord blood hematopoietic cell composition.

Several studies have demonstrated that cord blood (CB) unit composition is an important predictor of outcome after CB transplantation, with higher infused doses of nucleated cells (NC) or hematopoietic stem and progenitor cells being associated with faster engraftment and better overall survival. 1-3 Identification of factors predicting the hematopoiet-ic cell content of CB units is, therefore, an important issue for CB banking strategies. Large studies have reported several maternal, fetal and obstetrical factors impacting CB cell yield. 4-6 Recently, it has been documented in adult individuals that hematopoietic stem and progenitor cells circulate from the bone marrow to the peripheral blood according to a circadian rhythm, 7 leading to circadian variations in their concentrations in blood (reviewed by Mendez-Ferrer 8). Whether similar rhythmic release also occurs during fetal life, and whether time of day at which delivery occurs, may impact CB hematopoietic cell composition remain unknown. In this multicenter study, we analyzed factors that potentially influence the concentrations of NC and hematopoietic cells in a large series of CB samples and we observed an impact of time of day and month of delivery. Three University centers participated in this study. CB units were collected over four consecutive years as part of a CB banking project (Ethics Committee registration number: F93/20/1728), with written informed consents obtained from the mothers. Our standard procedures for CB banking required all units to be collected in utero after vaginal delivery of single-birth term babies (>36 weeks of gestational age). After collection, a 2-mL sample of CB was taken for complete blood counts, assessment of CD34 + cell concentration by flow cytometry and Colony-Forming Units (CFU) assays. Myeloid (CFU-GM) colonies were scored by all three centers whereas erythroid (Burst Forming Unit Erythroid, BFU-E) and multilineage (CFU-Mix) colonies were only assessed in one of the centers.