Uterine artery blood flow, fetal hypoxia and fetal growth

Abstract

Evolutionary trade-offs required for bipedalism and brain expansion influence the pregnancy rise in uterine artery (UtA) blood flow and, in turn, reproductive success. We consider the importance of UtA blood flow by reviewing its determinants and presenting data from 191 normotensive (normal, n = 125) or hypertensive (preeclampsia (PE) or gestational hypertension (GH), n = 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n = 37). Prior studies show that UtA blood flow is reduced in pregnancies with intrauterine growth restriction (IUGR) but whether the IUGR is due to resultant fetal hypoxia is unclear. We found higher UtA blood flow and Doppler indices of fetal hypoxia in normotensive women at high versus low altitude but similar fetal growth. UtA blood flow was markedly lower in early-onset PE versus normal high-altitude women, and their fetuses more hypoxic as indicated by lower fetal heart rate, Doppler indices and greater IUGR. We concluded that, despite greater fetal hypoxia, fetal growth was well defended by higher UtA blood flows in normal Andeans at high altitude but when compounded by lower UtA blood flow in early-onset PE, exaggerated fetal hypoxia caused the fetus to respond by decreasing cardiac output and redistributing blood flow to help maintain brain development at the expense of growth elsewhere. We speculate that UtA blood flow is not only an important supply line but also a trigger for stimulating the metabolic and other processes regulating feto-placental metabolism and growth. Studies using the natural laboratory of high altitude are valuable for identifying the physiological and genetic mechanisms involved in human reproductive success.

Keywords: Doppler velocimetry; brain sparing; fetal biometry; high-altitude adaptation; intrauterine growth restriction.

Figure 1.

(a) At sea level, maternal UtA blood at a pO₂ of 100 mmHg enters the intervillous space where it is stirred by oscillations of fetal villi and equilibrates with UtV blood at a pO₂ of 45 mmHg. Assuming a 10 mmHg gradient, blood reaching the fetal circulation has a pO₂ of 35 mmHg and, following fetal O₂ uptake, returns to the placenta at a pO₂ of 21 mmHg. (b) High altitude. Using the values reported by or extrapolated from Postigo et al. [21] at 3600 m, maternal UtA pO₂ is 55 mmHg, UmbV pO₂ is 28 mmHg and umbilical artery (UmbA) pO₂ is 16 mmHg. Assuming a 10 mmHg UtV–UmbV gradient, the UtV pO₂ would then be 38 mmHg. (Adapted from Battaglia & Meschia [20].)

Figure 2.

(a–d) Filled columns are mean ± s.e.m. values measured in cross-sectional samples of normal, healthy very high-altitude (4100–4300 m) pregnant Andeans at the week of gestation shown. Open columns are from cross-sectional samples of high-altitude Andeans diagnosed with PE or GH, with those diagnosed early (less than or equal to 34 weeks) or late (more than 34 weeks) shown. Grey filled circles are from 37 Andeans residing at low altitude (400 m) who were studied serially at weeks 20 and 36. (a) Bilateral UtA blood flow is higher in normal than early-onset PE women at high altitude, and higher in normal residents of high than low altitude. (b) FHR tends to be higher in normal than early- or late-onset PE/GH Andeans at high altitude and is higher in normal low- than high-altitude Andeans. (c) The ratio of the MCA PSV to the umbilical artery (UmbA) PSV is lower in normal than early-onset PE or late-onset PE/GH Andean residents of high altitude, especially at weeks 24 and 32 of gestation (asterisks). (d) The ratio of the MCA PI to the UmbA PI is lower in the normal high- than low-altitude women. The effect of advancing gestation (time) tends to differ in the normal versus PE/GH high-altitude groups, likely as the result of more variable values in the PE/GH subjects.