Physiological mechanisms of hyperventilation during human pregnancy

This study examined the role of pregnancy-induced changes in wakefulness (or non-chemoreflex) and central chemoreflex drives to breathe, acid–base balance and female sex hormones in the hyperventilation of human pregnancy. Thirty-five healthy women were studied in the third trimester (TM3; 36.3 ± 1.0 weeks gestation; mean ± S.D.) and again 20.2 ± 7.8 weeks post-partum (PP). An iso-oxic hyperoxic rebreathing procedure was used to evaluate wakefulness and central chemoreflex drives to breathe. At rest, arterialized venous blood was obtained for the estimation of arterial PCO2 (PaCO2) and [H+]. Blood for the determination of plasma strong ion difference ([SID]), albumin ([Alb]), as well as serum progesterone ([P4]) and 17β-estradiol ([E2]) concentrations was also obtained at rest. Wakefulness and central chemoreflex drives to breathe, [P4] and [E2], ventilation and V˙CO2 increased, whereas PaCO2 and the central chemoreflex ventilatory recruitment threshold for PCO2 (VRTCO2) decreased from PP to TM3 (all p < 0.01). The reductions in PaCO2 were not related to the increases in [P4] and [E2]. The alkalinizing effects of reductions in PaCO2 and [Alb] were partly offset by the acidifying effects of a reduced [SID], such that arterial [H+] was still reduced in TM3 vs. PP (all p < 0.001). A mathematical model of ventilatory control demonstrated that pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid–base balance, V˙CO2 and cerebral blood flow account for the reductions in PaCO2, [H+] and VRTCO2. This is the first study to demonstrate that the hyperventilation and attendant hypocapnia/alkalosis of human pregnancy results from a complex interaction of pregnancy-induced changes in wakefulness and central chemoreflex drives to breathe, acid–base balance, metabolic rate and cerebral blood flow.