Journal Article

Transcriptome analysis of early pregnancy vitamin D status and spontaneous preterm birth

McElrath, Thomas F., Weiss, Scott T., Mirzakhani, Hooman, Yadama, Aishwarya P., Litonjua, Augusto A.

2020

Overview

We conducted a literature review on the studies that investigated the relationship of preterm birth, including spontaneous preterm birth (sPTB), with vitamin D status. Overall, these studies demonstrated that the incidence of sPTB was associated with maternal vitamin D insufficiency in early pregnancy. However, the potential mechanisms and biological pathways are unknown. To investigate early pregnancy gene expression signatures associated with both vitamin D insufficiency and sPTB. We further constructed a network of these gene signatures and identified the common biological pathways involved. We conducted peripheral blood transcriptome profiling at 10-18 weeks of gestation in a nested case-control cohort of 24 pregnant women who participated in the Vitamin D Antenatal Asthma Reduction Trial (VDAART). In this cohort, 8 women had spontaneous preterm delivery (21-32 weeks of gestation) and 17 women had vitamin D insufficiency (25-hydroxyvitamin D < 30 ng/mL). We separately identified vitamin D-associated and sPTB gene signatures at 10 to 18 weeks and replicated the overlapping signatures in the mid-pregnancy peripheral blood of an independent cohort with sPTB cases. At 10-18 weeks of gestation, 146 differentially expressed genes (25 upregulated) were associated with both vitamin D insufficiency and sPTB in the discovery cohort (FDR < 0.05). Of these genes, 43 (25 upregulated) were replicated in the independent cohort of sPTB cases and controls with normal pregnancies (P < 0.05). Functional enrichment and network analyses of the replicated gene signatures suggested several highly connected nodes related to inflammatory and immune responses. Our gene expression study and network analyses suggest that the dysregulation of immune response pathways due to early pregnancy vitamin D insufficiency may contribute to the pathobiology of sPTB.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 25-Hydroxyvitamin D / Adult / Analysis / Asthma / Binding sites / Biochemistry / Biology and Life Sciences / Biotechnology industries / Birth / Blood / Calciferol / Case-Control Studies / Childbirth & labor / Cohort Studies / Computer and Information Sciences / Criminal investigation / Double-Blind Method / Female / Gene expression / Gene Expression Profiling / Genes / Genetic aspects / Genetic research / Gestation / Hospitals / Humans / Hypertension / Immune response / Immune system / Incidence / Infant, Newborn / Inflammation / Literature reviews / Maternal Health / Medical schools / Medicine / Medicine and Health Sciences / Peripheral blood / Physical sciences / Preeclampsia / Pregnancy / Pregnant women / Premature birth / Premature Birth - blood / Premature Birth - epidemiology / Premature Birth - genetics / Premature Birth - immunology / Premature infants / Protein Interaction Maps - genetics / Proteins / Signatures / sptb gene / Studies / Transcriptome - genetics / Vitamin D / Vitamin D - analogs & derivatives / Vitamin D - blood / Vitamin D - immunology / Vitamin deficiency / Vitamins / Womens health / Young Adult