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Objective: One hundred percent oxygen is given in pregnancy to improve fetal oxygenation, yet has been shown in both animal and human studies ex utero to increase cerebral vascular resistance. Adjusting end-tidal pCO2 (ET-pCO2) levels to normocapnic levels during hyperoxygenation offsets this effect in non-pregnant individuals. We aimed to evaluate the effect of maternal hyperoxygenation with and without maintaining normocapnia on the fetal and uteroplacental circulations in healthy near-term human pregnancies. Methods: Eight healthy pregnant women, serving as their own controls, sequentially breathed room air, breathed 100% oxygen, and underwent normocapnic hyperoxygenation (NH) in a three-phase experiment involving a tight-fitting facemask. Each phase lasted 10-15 min. After steady state had been reached, peak velocities and pulsatility index (PI) values were obtained from the uterine, umbilical and fetal middle cerebral arteries (MCA) by color/pulsed Doppler. In addition, maternal ventilation and ET-pCO2 were monitored. Results: One hundred percent oxygen induced maternal hyperventilation and hypocapnea. Uterine artery PI and peak systolic velocities were stable during 100% oxygen. In contrast, during NH uterine artery PI values decreased by 21% (P=0.04). Umbilical artery PI and peak velocities were stable during 100% oxygen; PI increased by 16% during NH (P=0.056), with no change in peak velocities. Peak MCA velocities decreased by 8% during 100% oxygen, and by 9.6% during NH, while MCA-PI decreased by 13% during 100% oxygen and by 21% during NH (P=0.06). Conclusions: Maternal and fetal circulations exhibit divergent responses to 100% oxygen and NH. While no change is observed in the uteroplacental circulation on 100% oxygen, decreased resistance and increased flow velocity are evident during NH. Increased umbilical artery PI during NH with no change in absolute velocities may suggest a reduction in fetoplacental blood flow. Maintaining normocapnia during hyperoxygenation does not appear to beneficially influence the circulation of the near-term human fetus as it does in non-pregnant individuals. [ABSTRACT FROM AUTHOR]