Effect of Increased Maternal Hemoglobin Oxygen Affinity on Fetal Growth in the Rat

Abstract

A disparity between fetal and maternal hemoglobin oxygen affinities (i.e., P50fetal<P50meternal) is believed to be important in facilitating oxygen transfer from maternal to fetal circulation. However, human females with high oxygen affinity mutant hemoglobins (P50meternal<P50fetal) have successfully borne children, calling into question the importance of the usual maternal/fetal P50 gradient. We have investigated the effect of artificially increased maternal hemoglobin oxygen affinity on fetal growth in the rat. Pregnant rats were exchange transfused with homologous blood on the ninth day of gestation, the experimental group receiving donor blood having P50 ≃ 15.0 mm Hg achieved by prior incubation with sodium cyanate. This changed mean maternal P50 from 41.1 to 24.6 mm Hg; the normal prenatal rat has P50 = 24.7 mm Hg due to low erythrocyte 2,3-DPG content. Parameters reflecting the adequacy of fetal oxygenation were examined on the 20th and 21st days of gestation and at term (22 days). Fetuses from the experimental group were significantly smaller on the 21st day (p < 0.001) and at term (p < 0.01), and this was accompanied by placental hypertrophy. There was no significant difference in fetal weight on the 20th day of gestation unless a second exchange transfusion was performed to further lower maternal P50. There was a trend towards erythrocytosis in the experimental group fetuses. We conclude that a narrowing of the P50 difference between mother and fetus has adverse effects on fetal wellbeing in the rat.