(OR20-04-26) Maternal Diet Quality in Pregnancy Is Associated With Angiogenic and Unfolded Protein Response Pathways in Human Placenta at Term

Objectives: Maternal diet and body composition during pregnancy independently influence child health outcomes. While a large body of evidence has examined the impact of maternal obesity on the placenta, the links between maternal diet quality and placental gene expression is less understood. Here we examined associations between diet quality over pregnancy and placental gene expression at term using transcriptomic approaches.

Methods: Placenta were collected as part of a longitudinal study of mothers and infants (NCT01131117). Maternal anthropometrics, dietary intake (3 d food records) were collected for each trimester. Diet quality was summarized using the Healthy Eating Index (HEI-2015) and averaged over pregnancy. Placental gene expression via strand-specific mRNA-seq was available for 141 women. Data analyses were carried out using the STAR-limma pipeline. Multiple linear regression was utilized to assess relationships between HEI score and gene expression, while adjusting for maternal age and BMI. Gene Ontology biological processes and gene-set enrichment analysis were utilized for DEG interpretation.

Results: HEI-2015 values in pregnancy averaged 47.2 ± 7.1 (mean ± SD, range 32.3 - 66.0, Q1=42.5, Q3=51.3). In linear regression models, HEI-2015 values were positively associated with maternal age (ß/CI 0.49 yr, 0.16 - 0.83, p=0.004) and negatively associated with pre-pregnancy BMI (ß/CI -0.31, -0.61 - 0.01, p=0.04. Linear regression of mRNA expression with HEI-2015 (adjusting for BMI and age) identified significant association with 1,443 transcripts (adj p< 0.1, min ß=0.01). Positively associated genes were enriched for blood vessel morphogenesis, angiogenesis and vasculature development (q-value < 0.00001). Of note, expression of VEGFA, TEAD2, DLL4, and MFGE8 were positively associated with maternal HEI (p < 0.05). Conversely, genes involved in membrane lipid processes, ER to Golgi transport and response to ER stress were significantly enriched among negatively associated genes, indicating lower burden on protein-folding pathways.

Conclusions: In a cohort of well-characterized pregnant women, maternal diet quality was associated with genes involved in critical functional pathways in the placenta. The findings suggest that diet quality may be an important modifier of health outcomes in pregnancy.

Funding Sources: USDA-ARS