Approximately 40% of pregnant women consume alcohol, which crosses the placenta leading to increased fetal and neonatal complications such as growth restriction and stillbirth. Prior in-vitro studies suggest that acute ethanol exposure to the placenta induces a pressor effect on placental vasculature, which may decrease fetal oxygen delivery,¹ but the chronic effects on in-vivo placental perfusion and oxygenation are not known. We have recently developed a novel MRI method that uses the blood oxygenation level dependent (BOLD) effect for quantifying placental oxygenation and perfusion in-vivo through measurements of placental water T₂*.² Although prior studies have used MRI to semi-quantitatively assess placental oxygenation in pregnancy, it has not been quantitated or directly linked to placental perfusion in-vivo. This study utilizes a pregnant nonhuman primate model (NHP) model to assess the effects of first trimester ethanol exposure on placental perfusion with our new MRI-based technique and correlate these results with placental blood flow by conventional Doppler ultrasound (D-US). : Time-mated pregnant macaques (n=6) were divided into 2 treatment groups: control (n=3) and ethanol exposed (n=3). Animals were given either 1.5g/kg/day of ethanol (equivalent to 6 drinks per day) or an isocaloric control fluid through gestational day 60 (G60, term is 168 days). On G110, all animals were sedated with 1% isoflurane and underwent D-US (GE Voluson 730) followed by MRI. D-US was performed to measure uterine artery and umbilical vein velocimetry and diameter to calculate uterine artery volume blood flow (cQuta) and placental volume blood flow (cQuv).³ Multi-slice, multi-echo spoiled gradient echo images covering the entire placenta were acquired on a 3T Siemens TIM Trio scanner and were used to compute maps of T₂*. The methods described by Schabel et al. were used to determine the number of spiral artery sources and a parameter Ψ(=F/ν_iPS) that is equal to the total spiral artery flow (F) normalized by the product of intervillous volume fraction (ν_i) and fetal villous oxygen permeability surface area product (PS). The sum of this parameter over all sources, ∑Ψ_i, was calculated for comparison to uterine artery and placental volume flow values obtained by D-US.

Fetal biparietal diameter (35 vs. 39cm), cerebral cortex surface area (5970 vs. 6424 mm²) fetal weight (175.1 vs. 217.1g), and mean placental weight (64 vs. 75g) were decreased in ethanol exposed animals compared with controls. By D-US, we demonstrated a reduction in cQuta (148 vs. 341 ml/min) and cQuv (15 vs. 22 ml/min) and increased umbilical artery (1.68 vs. 1.22) and uterine artery (0.82 vs. 0.65) pulsatility indices s in ethanol exposed animals vs. controls.

MRI confirmed that placental blood flow and fetal oxygen transport was decreased in the ethanol exposed group (Figure 1) (Figure 2a and b). Histograms of T₂* computed over the entire placenta (normalized to total placental volume) indicate the fraction of placenta that is perfused with highly oxygenated blood (high T₂* values) vs. deoxygenated blood (low T₂* values). Control animals demonstrated a significantly greater fraction of higher T₂* values compared to the ethanol exposed animals, demonstrating decreased fetal oxygen supply in the latter group (Figure 3). Moreover, D-US and MRI measurements of maternal perfusion of the placenta (cQuta vs. ∑Ψ_i) were strongly correlated, r=0.91 (p=0.01) (Figure 4).

D-US detected impaired maternal perfusion of the placenta and increased vascular resistance. Our novel MRI-method confirmed our D-US findings and was able to quantify placental oxygenation and directly correlate it with placental perfusion in-vivo. The MRI-based analysis will enable further analyses of placental perfusion on the level of individual spiral arteries. The findings reported here suggest that cessation of alcohol consumption early in pregnancy does not prevent subsequent adverse fetal affects. Chronic first trimester prenatal ethanol exposure results in reduced maternal perfusion of the placenta and fetal oxygen availability. Disrupted placental function is associated with impaired fetal growth and development.