Fetal Hemoglobin in the Maternal Circulation - Contribution of Fetal Red Blood Cells

The major hemoglobin (Hb) during fetal life is fetal Hb (Hb F). It is mostly replaced by adult Hbs before birth and during the first year of life. In adults, where Hb F comprises <2.0% of the total Hb, it is not homogenously distributed among the red blood cells (RBCs) but is concentrated in a few RBCs, termed F-cells. Interestingly, for reasons that are unclear, Hb F increases in the maternal circulation during pregnancy. This increased Hb F could have two potential origins that are not mutually exclusive: A) maternal origin, due to inducing environment of Hb F in the maternal erythroid precursors; B) fetal origin, due to fetal cells crossing the placenta and entering the maternal circulation. The question we present herein is whether the observed increased Hb F in the maternal circulation during pregnancy is, at least partially, derived from the fetal origin. Peripheral blood was obtained from normal neonates (1-3 days old), adult men and pregnant and non pregnant women. The RBCs were stained for Hb F and carbonic anhydrase (CA) using a fetal cell count kit and analyzed by flow cytometry. Fetal and adult F-cells were distinguished by their expression of Hb F and CA. Fetal F-cells were Hb F⁺⁺/CA^-, while adult F-cells were Hb F⁺/CA⁺. Comparing pregnant and non pregnant women samples (n = 10), we found six samples of pregnant women with 0.2-1.7% fetal cells, but none in the non pregnant group. These results support the possibility that at least part of the increase in Hb F during pregnancy is due to fetal cells entering the maternal circulation.