Pro-inflammatory immune cell gene expression during the third trimester of pregnancy is associated with shorter gestational length and lower birthweight.

PROBLEM: Altered maternal immune function predicts risk for shorter gestation and low birthweight. Few studies examine associations between prenatal immune cell gene expression and gestational length or birthweight. No studies examine which cell types drive associations. The purpose of this study is to explore associations between peripheral blood immune cell gene expression and gestational length and birthweight, using transcript origin analysis.

METHOD OF STUDY: Eighty-nine women were drawn from the Community Child Health Network cohort. Third trimester maternal dried blood spots were used for genome-wide transcriptional (mRNA) profiling. Gestational length and birthweight were obtained from medical charts. Covariates were age, race/ethnicity, pre-pregnancy body mass index, smoking, gestational age at blood sampling, and pregnancy infections. Associations between gene expression profiles and gestational length and birthweight were tested using general linear models. The Transcription Element Listening System (TELiS) bioinformatics analysis quantified upstream transcription factor activity. Transcript origin analysis identified leukocyte subsets mediating observed effects.

RESULTS

Shorter gestation was predicted by increased NF-kB (TFBM ratio = -0.582 ± 0.172, P < .001) and monocyte activity (diagnosticity score = 0.172 ± 0.054, P < .001). Longer gestation was associated with increased dendritic cell activity (diagnosticity score = 0.194 ± 0.039, P < .001). Increased AP-1 activity predicted lower birthweight (TFBM ratio = -0.240 ± 0.111, P = .031). Dendritic cells and CD4+ and CD8+ T cells predicted birthweight-related gene expression differences (diagnosticity score P's < 0.021).

CONCLUSION

Higher third trimester pro-inflammatory gene expression predicted shorter gestation and lower birthweight. Variations in monocyte and dendritic cell biology contributed to both effects, and T-cell biology contributed to higher birthweight. These analyses clarify the role of myeloid/lymphoid lineage immune regulation in pregnancy outcomes.