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While chronic hypoxia has been recognized as the principal causative factor for decreasing birth weight at high altitude, unknown is whether fetal fat accretion and vascular function are affected.Colorado women with normal singleton pregnancies (18 Denver residents, 1,600 m; 24 Leadville residents, 3,100 m) were studied longitudinally from 20 to 36 weeks gestation. Fetal biometry was used to obtain axial images for assessing mid-upper arm and mid-thigh subcutaneous tissue mass (MUA and MUL SQ) and Doppler waveform analysis conducted to measure indices of vascular function in the fetal umbilical arteries (UmbA), umbilical vein (UmbV), middle cerebral artery (MCA), and ductus venosus (DV). SAS PROC MIXED was used to compare altitudes with P0.05 considered significant and trends present when 0.05P0.10.The 3,100 m vs. 1,600 m babies weighed less at birth. Third trimester fetal biometry, MUA SQ and MUL SQ were somewhat lower, but neither the biometry nor the SQ altitudinal differences attained statistical significance. Greater prepregnant maternal BMI tended to decrease MUA SQ (P = 0.07) and increase MUL SQ (P = 0.07). UmbA S/D ratios decreased and UmbV flow increased with advancing gestation (both P0.001). Altitude did not affect the UmbA or MCA systolic/diastolic ratios (S/D), MCA peak-systolic velocity, UmbV flow, or the DV systolic/atrial flow ratio.The hypoxia of residence at high compared to moderate altitude lowered birth weight but did not significantly alter MUA or mid-thigh fetal subcutaneous tissue mass or Doppler indices of vascular function.

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 (QUA). 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. QUAwas lower in early-onset (≤34 wk) PE or GH than in NORM, but was normal in late-onset (>34 wk) illness. Left QUAwas consistently greater than right in NORM, but the pattern reversed in PE. Although QCIand QEIwere higher in PE and GH than NORM, the fraction of QCIdistributed 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 QUA( R2= 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 QUAand restricted fetal growth in PE and GH. These are, to our knowledge, the first quantitative measurements of QUAand pelvic blood flow in early- vs. late-onset PE in high-altitude residents.

Reduced uteroplacental blood flow is hypothesized to play a key role in altitude-associated fetal growth restriction. It is unknown whether reduced blood flow is a cause or consequence of reduced fetal size. We asked whether determinants of uteroplacental blood flow were altered prior to reduced fetal growth and whether vasoactive and/or angiogenic factors were involved. Women residing at low (LA; 1600 m, n = 18) or high altitude (HA; 3100 m, n = 25) were studied during pregnancy (20, 30, and 36 wk ) and 4 mo postpartum (PP) using Doppler ultrasound. In each study, endothelin (ET-1), nitric oxide metabolites (NO x), soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PlGF) levels were quantified. At HA, birth weights were lower ( P < 0.01) and small-for-gestational age was more common ( P < 0.05) compared with LA. HA was associated with lower uterine artery (UA) diameter ( P < 0.01) and blood flow ( P < 0.05). Altitude did not affect ET-1, sFlt-1 or PlGF; however, ET-1/NO x was greater and NO x lower during pregnancy and PP at HA vs. LA. ET-1/NO x was negatively associated with birth weight (20 wk, P < 0.01; 36 wk, P = 0.05) at LA and HA combined. At HA, UA blood flow (30 wk) was positively associated with birth weight (†). UA blood flow and ET-1/NO x levels accounted for 45% (20 wk) and 32% (30 wk) of birth weight variation at LA and HA combined, primarily attributed to effects at HA. We concluded that elevated ET-1/NO x and altered determinants of uteroplacental blood flow occur prior to altitude-associated reductions in fetal growth, and therefore, they are likely a cause rather than a consequence of smaller fetal size.

Objective This study was undertaken to evaluate the association between uterine artery Doppler velocimetry performed between 10 and 14 weeks gestation and intrauterine growth restriction (IUGR). Study design Uterine artery Doppler velocimetry data were collected on 1067 women enrolled in the FASTER trial at the University of Colorado site. The data were analyzed by using univariate and multivariable logistic regression analysis. Results The uterine artery mean resistance index (RI) for the entire cohort was equal on the right and left sides (0.59 ± 0.14). Of the 1067 women, 34.2% had unilateral or bilateral diastolic notches, 1 notch was observed in 23.8%, and bilateral notches in 10.4%. Women with a high uterine artery mean RI (≥75th percentile) were 5.5 times more likely to have IUGR (95% CI 1.6-18.7). There was no significant relationship between notching and IUGR. Conclusion Elevated first trimester uterine artery mean RI is significantly associated with IUGR.