Advertisement

28: First trimester alcohol exposure alters placental perfusion and fetal oxygen availability affecting fetal growth and development in a non-human primate model

      Objective

      Prenatal alcohol exposure leads to impaired fetal growth, brain development, and stillbirth. The placenta likely contributes to these adverse outcomes, but the mechanisms and specific vasoactive effects of alcohol linking placental perfusion and oxygenation to impaired fetal development are not known. Recently, we developed MRI techniques in non-human primate models to estimate placental oxygen reserve by measurements of T2*, and perfusion using dynamic contrast enhanced (DCE) MRI. Our objective was to evaluate the adverse effects of first trimester alcohol exposure on placental outcomes and to characterize fetal brain development in-vivo.

      Study Design

      Timed-pregnant Rhesus macaques (n=12) were divided into 2 groups: control (CON, n=6) and ethanol exposed (EE, n=6). Animals were given either 1.5g/kg/day of ethanol (equivalent to 6 drinks/day) or an isocaloric control fluid from pre-conception until gestational day 60 (G60, term is G168). All underwent Doppler ultrasound (D-US) followed by MRI consisting of T2* and DCE measurements. D-US was used to measure uterine artery (Uta) and umbilical vein velocimetry and diameter to calculate Uta volume blood flow (cQuta) and placental volume blood flow (cQuv). After non-invasive imaging, animals underwent C-section delivery for placenta collection and fetal necropsy at G110 (n=6) or G135 (n=6).

      Results

      By D-US, cQuta and cQuv were reduced at G110 and G135 in EE vs. CON (Fig 1). Reductions in placental blood flow were evident by DCE-MRI (Fig 1). As we demonstrated recently, T2* values vary throughout the placenta, and reveal regions of high oxyhemoglobin concentration (long T2*) and high deoxyhemoglobin concentration (short T2*). Distributions of T2* throughout the placenta (Fig 2) shows global reduction in T2* (and hence blood oxyhemoglobin) in EE vs. CON at G110 and G135. Fetal brain measurements were decreased at G110, but similar at G135 in EE vs. CON (Fig 1).

      Conclusion

      Chronic first trimester EE reduces placental perfusion and impairs fetal growth and development apparent at mid-gestation. However, both placental function and fetal brain development improved by late-gestation suggesting that placental adaptation to early perturbations allows for compensated placental function and maintenance of fetal growth.
      Figure thumbnail fx1
      Figure thumbnail fx2