Dataset Information

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study.

ABSTRACT:

Background

Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.

Methods

As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip(R) Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.

Results

A total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.

Conclusions

PTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.

SUBMITTER: Enquobahrie DA

PROVIDER: S-EPMC2799378 | biostudies-literature | 2009 Dec

REPOSITORIES: biostudies-literature

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Publications

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study.

Enquobahrie Daniel A DA Williams Michelle A MA Qiu Chunfang C Muhie Seid Y SY Slentz-Kesler Kimberly K Ge Zhaoping Z Sorenson Tanya T

BMC pregnancy and childbirth 20091210

<h4>Background</h4>Preterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.<h4>Methods</h4>As part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 w ...[more]

PMID: 20003277

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Project description:ObjectiveTo determine the association between depth of excision of cervical intraepithelial neoplasia and risk of preterm birth.DesignCase-control study nested in record linkage cohort study.Setting12 hospitals in England.ParticipantsFrom a cohort of 11 471 women with at least one histological sample taken at colposcopy and a live singleton birth (before or after colposcopy), 1313 women with a preterm birth (20-36 weeks) were identified and frequency matched on maternal age at delivery, parity, and study site to 1313 women with term births (38-42 weeks).Main outcome measuresRisk of preterm birth and very/extreme preterm birth by depth of excisional treatment of the cervical transformation zone.ResultsAfter exclusions, 768 preterm births (cases) and 830 term births after colposcopy remained. The risk of preterm birth was no greater in women with a previous small (<10 mm) excision (absolute risk 7.5%, 95% confidence interval 6.0% to 8.9%) than in women with a diagnostic punch biopsy (7.2%, 5.9% to 8.5%). Women with a medium (10-14 mm) (absolute risk 9.6%; relative risk 1.28, 0.98 to 1.68), large (15-19 mm) (15.3%; 2.04, 1.41 to 2.96), or very large (≥ 20 mm) excision (18.0%; 2.40, 1.53 to 3.75) had a higher risk of preterm delivery than those with small excision. The same pattern was seen in 161 women with very/extremely preterm births (20-31 weeks) and with increasing volume excised. Most births were conceived more than three years after colposcopy, and the risk of preterm delivery did not seem to depend on time from excision to conception.ConclusionsThe risk of preterm birth is at most minimally affected by a small excision. Larger excisions, particularly over 15 mm or 2.66 cm(3), are associated with a doubling of the risk of both preterm and very preterm births. The risk does not decrease with increasing time from excision to conception. Efforts should be made to excise the entire lesion while preserving as much healthy cervical tissue as possible. Close obstetric monitoring is warranted for women who have large excisions of the cervical transformation zone.

Dataset Information

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study.

Background

Methods

Results

Conclusions

Publications

Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study.

Similar Datasets

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