Fraser Fellows

Fetal heart rate and activity patterns in growth-retarded fetuses: Changes after vibratory acoustic stimulation

Seventeen pregnant women who subsequently were delivered of infants with birth weights less than the third percentile were studied for examination of fetal heart rate and fetal activity patterns before and after a 5-second external vibratory acoustic stimulation. None of the fetuses was acidotic at birth. A reduced time was noted during which accelerations in heart rate occurred (50% less) and long-term fetal heart rate variability (25% less) in small for gestational age fetuses compared with age-matched, normally grown fetuses. The incidence of gross fetal body movements was significantly lower (40% less) in small for gestational age fetuses than in those who were appropriate for gestational age. Fetal heart rate and fetal activity patterns after stimulation with the electronic artificial larynx in small for gestational age fetuses were similar to those of appropriate for gestational age fetuses.

Circulating hematopoietic stem cells serve as novel targets for in utero gene therapy

In utero gene therapy has been proposed as a method for permanent correction of somatic disorders that affect the hematopoietic system before disease initiation (1, 2). However, clinical trials using transplantation of allogenic fetal liver, bone marrow, or adult stem cells have been unsuccessful, largely due to the failure of sustained hematopoietic reconstitution in fetal recipients (3). Here, we reveal that retroviral transduction of unique repopulating stem cells found in the human fetal circulation is superior to full‐gestation cord blood or adult sources. In contrast to postnatal human stem cells, the fetal circulation is highly enriched for actively cycling blood stem cells, thereby forming the basis for enhanced transduction. Our findings indicate that active, transducible hematopoietic reconstituting cells are present in the circulation of the human fetus and that they represent novel target cells for future in utero gene therapy trials using autologous transplantation.