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 ¼ 125) or hypertensive ( preeclampsia (PE) or gestational hypertension (GH), n ¼ 29) Andean residents of very high (4100-4300 m) or low altitude (400 m, n ¼ 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.

Ultrasound prediction of abnormal infant development in hypertensive pregnant women in the second and third trimester

“…Our data are similar to previously published PI values of 0.80–0.73 in healthy women vs 1.47–1.43 in pre-eclampsia/gestational hypertension patients between 28 and 32 gestational weeks in high altitudes14, and 1.42 ± 0.23 in women with persistent hypertension between 26–28 gestational weeks15.…”

Ambient temperature and air quality in relation to small for gestational age and term low birthweight

“…The second and third trimesters are important times for fetal growth (Buck Louis et al, 2015). As extreme temperature may affect uterine blood flow and placental exchange necessary for fetal growth (Browne et al, 2015; Prada and Tsang, 1998), disruption to the mechanism needed for proper growth during these time windows would have the greatest impact. In addition, the fact that whole-pregnancy average was significantly associated with low birthweight suggests that chronic exposures to high/low temperature maybe more important with respect to adverse birth outcomes than previously thought.…”

“…Previous research suggests that exposures to extreme temperature as well as high air pollution may increase oxidative stress and systemic inflammation in the general population (Ghio et al, 2012; Kahle et al, 2015; Moller et al, 2014). Although mechanistic studies in pregnant women are still scarce in relation to these environmental risk factors, exposures during pregnancy may decrease uterine blood flow, placental fetal exchange and ultimately slow fetal growth (Biberoglu et al, 2016; Browne et al, 2015; Prada and Tsang, 1998; Slama et al, 2008). Consistent with this potential biologic mechanism, extreme ambient temperature and air pollution exposure have been linked to adverse birth outcomes such as low birthweight and preterm birth, but their association with SGA and tLBW— is still unclear given the scarcity of literature on this topic and the inconsistent findings across pollutants and studies (Auger et al, 2014; Shah and Balkhair, 2011; Strand et al, 2011).…”

Neonatal Oxygenation, Pulmonary Hypertension, and Evolutionary Adaptation to High Altitude (2013 Grover Conference series)

“…43 One factor influencing P pa during adulthood is perinatal hypoxia, as shown by human and experimental animal studies in which greater hypoxia in utero or during the neonatal period increased the reactivity of the pulmonary vasculature to hypoxia later in life. 44,45 Perinatal hypoxia is greater at high than at low altitudes, as demonstrated by the known reduction in birth weight resulting from slowed fetal growth, 46 Doppler indices of fetal hypoxia, 47 and lower postnatal arterial O 2 saturations (SaO 2 's). 48 Perinatal hypoxia also varies among populations; the altitude-associated reductions in fetal growth are only half (45%) as great in Tibetans or Andeans as in Han or Europeans residing at the same altitudes (Fig.…”