3: Maternal high fat diet decreases placental blood flow and increases the frequency of stillbirth in a non-human primate model of excess nutrition


      Pre-pregnancy maternal obesity confers an increased risk of stillbirth; however, the mechanisms whereby excess maternal nutrition affects the placenta are poorly understood. We used a nonhuman primate (NHP) model to determine the effect of chronic high-fat diet (HFD) on uterine and placental hemodynamics and placental histology.

      Study Design

      A total of 24 adult female Japanese macaques were separated into 2 groups: the control (CTR) group (n=9) was fed a standard monkey chow that provides 14% of calories from fat. The HFD group was maintained on a diet that supplies 32% calories from fat. On gestational day 120 (term 165 days), Doppler ultrasound was used to calculate uterine artery volume blood flow (cQuta), placental volume blood flow (cQuv), and umbilical artery pulsatility index (UA PI). The macaques were delivered on day 130 by cesarean section. The placenta samples were processed and stained by H&E and were graded by a placenta pathologist blinded to the treatment group. One-way ANOVA was used for statistical analysis.


      Animals fed the HFD segregated into diet resistant (HFD-R, n=6), or diet sensitive (HFD-S, n=9) based on body weight and insulin resistance. HFD animals showed a 38-56% reduction in cQuta (p<0.05). HFD consumption by obese mothers with hyperinsulinemia (HFD-S) led to a 32% reduction in cQuv (p<0.05) and an increased incidence of placental infarctions (p<0.05). In the HFD-S animals there were 7 stillbirths out of 20 pregnancies (p<0.05) compared with 1 stillbirth out of a total of 26 CTR pregnancies, and 1 stillbirth out of a total of 13 HFD-R pregnancies. The UA PI was not significantly different amongst the groups.


      A HFD, independent of obesity, decreases cQuta. Maternal obesity and insulin resistance further exacerbates the placental dysfunction and results in an increased frequency of stillbirth. Our results suggest that poor nutrition during pregnancy and not just obesity is a risk factor for adverse obstetric outcomes.