Maternal Caffeine Administration and Cerebral Oxygenation in Near-Term Fetal Sheep

Abstract

The authors test the null hypothesis that maternal caffeine administration will not significantly alter fetal cerebral oxygenation. The authors measured fetal arterial blood gases, cortical tissue O(2) tension (tPO(2)), sagittal sinus blood gases, and laser Doppler cerebral blood flow in response to a 30-minute caffeine infusion (400 mg intravenously) into 7 near-term pregnant ewes, and they calculated fractional O(2) extraction and relative cerebral metabolic rate for O(2) (CMRO(2)). Following maternal caffeine infusion, both fetal cortical tPO(2) and sagittal sinus (HbO(2)) decreased significantly, from 10.7 +/- 0.9 to 6.8 +/- 1.1 Torr and from 46% +/- 2% to 37% +/- 6%, respectively. This was associated with significant 20% to 30% increases in fractional O(2) extraction and CMRO( 2). Fetal arterial blood gas values did not change significantly. In conclusion, maternal caffeine administration significantly decreases cerebral oxygenation without affecting systemic oxygenation in fetal sheep. The authors speculate that for a fetus that may be otherwise compromised, this increase in CMRO(2) with decreased cortical tPO(2) could present a problem.

Cerebral vascular regulation and brain injury in preterm infants

“…The maximum level of COE attainable in preterm infants, at which the oxygen extraction mechanism is exhausted and unable to meet demand for oxygen, remains unknown. In fetal lambs, maternal caffeine infusion increases fetal cerebral oxygen consumption, which is met by minimally increased CBF and a 20 -30% increase in COE (199). In fetal lambs and ventilated preterm lambs subjected to reduced cerebral oxygen delivery, COE values of up to 60% have been measured (7,149), close to values found in adult patients with head injury (123).…”

Modest maternal caffeine exposure affects developing embryonic cardiovascular function and growth

“…Tomimatsu et al (42) recently reported that acute maternal caffeine exposure reduces fetal cerebral blood flow and local brain oxygen tension. These authors also described that local brain oxygen consumption increases without changes in circulating blood gas oxygen tension in near-term ewe fetuses (42).…”

“…Tomimatsu et al (42) recently reported that acute maternal caffeine exposure reduces fetal cerebral blood flow and local brain oxygen tension. These authors also described that local brain oxygen consumption increases without changes in circulating blood gas oxygen tension in near-term ewe fetuses (42). We found in the present study that with recurrent maternal caffeine exposure, the crown-rump length, upper limb size, and wet body weight of caffeine-treated ED 18.5 fetuses were smaller than sham fetuses, whereas the head size was unaffected.…”

The Fetal Cerebral Circulation: Three Decades of Exploration by the LLU Center for Perinatal Biology

“…This novel method helped illustrate the involvement of NO in hypoxic vasodilatation of fetal cerebral blood flow [124], the ability of only 4 min of umbilical cord occlusion to ablate cerebral autoregulation [125], the absence of ischemic preconditioning responses in fetal cerebral circulation responses to repeated cord occlusions [126], the indirect role of prostanoids in fetal cerebrovascular responses to hypoxia [127], the effects of hypercapnia on cerebral oxygenation in the fetus [128], the positive effects of maternal oxygen supplementation on fetal cerebral oxygenation [129], and the ability of the fetal brain to adapt to chronic hypoxia through modification of oxygen extraction [130]. Similar studies have also demonstrated the ability of maternal caffeine to decrease fetal cortical oxygen tensions [131], the potential effects of maternal hypocapnia, CO 2 supplementation, and hypercapnia on fetal cerebral oxygenation [132, 133], and finally, the tight coupling between ECoG state with cerebral oxygen consumption and cerebral blood flow in the term fetal brain under both normoxic and hypoxic conditions [134]. As a whole, this group of studies helps depict the fetal cerebral circulation as a highly dynamic system capable of adaptation and homeostasis mediated by mechanisms unique to the fetus.…”