Abstract

Objectives. To test whether preconception and prenatal stress predicts inflammatory gene expression in a manner consistent with risk for inflammation-linked pregnancy complications, particularly preterm birth. Methods. Stressful life events that occurred over the previous year were assessed at 6 months preconception and during the third trimester of pregnancy in 116 women recruited from 5 US sites by the Community Child and Health Network. Third trimester dried blood spots were assayed for genome-wide transcriptional profiles using RNAseq. Bioinformatics analyses assessed activity of pro-inflammatory transcription factors adjusting for age, race/ethnicity, pre-pregnancy BMI and prenatal infection. Results. Women who had more than two prenatal stressful life events (high stress) had higher expression of a 19-gene pro-inflammatory composite score, b=.204 log2 mRNA ± SE.058, corresponding to 15% elevation, p=.003, compared to women with two or fewer (low stress). Bioinformatic analyses of 387 gene transcripts showing >1.5-fold difference in expression between high vs. low prenatal stress women implicated increased activity of pro-inflammatory transcription factors, NF-kB (2.28-fold ± .15-fold, p .073. Conclusions. Prenatal stress was associated with up-regulated inflammatory gene expression in the third trimester of pregnancy, but preconception stress was not. Such effects may represent one pathway by which stress might contribute to increased risk for inflammation-linked, adverse pregnancy outcomes, such as preterm birth.

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