High-end arteriolar resistance limits uterine artery blood flow and restricts fetal growth in preeclampsia and gestational hypertension at high altitude

Abstract

The reduction in infant birth weight and increased frequency of preeclampsia (PE) in high-altitude residents have been attributed to greater placental hypoxia, smaller uterine artery (UA) diameter, and lower UA blood flow (Q(UA)). This cross-sectional case-control study determined UA, common iliac (CI), and external iliac (EI) arterial blood flow in Andeans residing at 3,600-4,100 m, who were either nonpregnant (NP, n = 23), or experiencing normotensive pregnancies (NORM; n = 155), preeclampsia (PE, n = 20), or gestational hypertension (GH, n = 12). Pregnancy enlarged UA diameter to ~0.62 cm in all groups, but indices of end-arteriolar vascular resistance were higher in PE or GH than in NORM. Q(UA) was lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left Q(UA) was consistently greater than right in NORM, but the pattern reversed in PE. Although Q(CI) and Q(EI) were higher in PE and GH than NORM, the fraction of Q(CI) distributed to the UA was reduced 2- to 3-fold. Women with early-onset PE delivered preterm, and 43% had stillborn small for gestational age (SGA) babies. Those with GH and late-onset PE delivered at term but had higher frequencies of SGA babies (GH=50%, PE=46% vs. NORM=15%, both P < 0.01). Birth weight was strongly associated with reduced Q(UA) (R(2) = 0.80, P < 0.01), as were disease severity and adverse fetal outcomes. We concluded that high end-arteriolar resistance, not smaller UA diameter, limited Q(UA) and restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of Q(UA) and pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

Fig. 1.

Shown are representative Doppler flow-velocity waveforms from uterine (UA), common iliac (CI), and external iliac (EI) arteries. UA blood flow (Q_UA) is continuous throughout the cardiac cycle and demonstrates a low-resistance pattern characterized by high peak systolic (PSV), end-diastolic (EDV), and mean flow (MFV) velocities. Q_CI and Q_EI demonstrate a high-resistance triphasic, pulsatile pattern with an antegrade midsystolic peak (PSV) followed rapidly by a retrograde minimum early-diastolic velocity (MDV), and then by resumption of forward flow that tapers off in late diastole.

Fig. 2.

Blood flow in the UA, CI, and EI arteries in nonpregnant controls (Non Preg), normotensive pregnant women who delivered at term (NT) or preterm (NPT), and women with gestational hypertension (GH) or preeclampsia (PE) who were ≤34 wk or >34 wk of pregnancy at the time of ultrasound study. A: compared with NT, uterine artery blood flow (Q_UA) was lower in NPT and markedly reduced in early-onset but not in late-onset GH and PE. B and C: women who developed PE and GH had greater pregnancy-associated increases in Q_CI and Q_EI than NT. P < 0.01 in *NT vs. NPT, GH, or PE; †≤34 wk vs. >34 wk; ‡Nonpregnant vs. pregnant; and §GH vs. PE.

Fig. 3.

Left and right Q_UA were equal in nonpregnant women but dissimilar during pregnancy. Left Q_UA (A) was consistently higher than the right (B) in normotensive women who delivered at NT and in late-onset GH. The reverse occurred in normotensive women who delivered NPT and in women with PE, with left Q_UA being much lower than the right Q_UA. P < 0.01 in *NT vs. NPT, GH, or PE; †≤34 wk vs. >34 wk; ‡Nonpregnant vs. pregnant; and §GH vs. PE.

Fig. 4.

CI artery blood flow is redistributed to favor the UA during pregnancy. A: compared with normotensive women who delivered at NT, UA relative to CI blood flow (UA/CI ratio) was reduced in normotensive women who delivered NPT and in women with GH or PE. B: EI relative to CI blood flow (EI/CI ratio) decreased during pregnancy and was lowest in GH, early-onset PE, and NT >34 wk. P < 0.05 in *NT vs. NPT, GH, or PE; †≤34 wk vs. >34 wk; ‡Nonpregnant vs. pregnant; and §GH vs. PE.

Fig. 5.

Uterine artery (UA) artery blood flow (Q_UA) at the time of ultrasound study are strongly related to average birth weight when comparing women who remained normotensive and delivered at term (NT) or preterm (NPT), and those who developed GH or PE. Reduced Q_UA before 34 wk was associated with lower birth weight and an increased risk of premature delivery. The solid line with dotted 95% CI shows the overall correlation, and the R² value of 0.80 indicates that 80% of the variation in birth weight can be explained by Q_UA across all groups. P < 0.05 in *NT vs. NPT, GH, or PE; †≤34 wk vs. >34 wk; and §GH vs. PE.