A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery

Ngo, Thuy; Moufarrej, Mira N.; Rasmussen, Marie-Louise Hee; Camunas-Soler, Joan; Pan, Wenying; Okamoto, Jennifer; Neff, Norma; Liu, Keli; Wong, Ronald J.; Downes, Katheryne; Tibshirani, Robert; Shaw, Gary M.; Skotte, Line; Stevenson, David K.; Biggio, Joseph; Elovitz, Michal A.; Melbye, Mads; Quake, Stephen R.

doi:10.1101/212910

Cited by 2 publications

(3 citation statements)

References 29 publications

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“…Our study provides insight into potential immune mechanisms that could drive preterm birth, but did not identify a clear biomarker for preterm birth akin to the signature recently identified using analysis of cell-free DNA (31). In fact, it will be important to validate such signatures in cohorts drawn from a range of geographic areas, with a particular focus on Africa and Asia where preterm birth is most prevalent.…”

Section: Discussionmentioning

confidence: 79%

“…Consistent with the idea that preterm birth is an inflammatory state, monocytes from women with a history of preterm birth demonstrated enhanced inflammatory responses in response to stimulation in vitro (30). More recently, significant progress was made in identifying signatures predictive of preterm birth and delivery timing using cell-free RNA in the blood (31,32). The studies performed to date have varied in the specific gene signatures identified, and in fact, there has been very poor agreement between studies in the genes identified (33).…”

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confidence: 87%

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Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

et al. 2020

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Specific causes of preterm birth remain unclear. Several recent studies have suggested that immune changes during pregnancy are associated with the timing of delivery, yet few studies have been performed in low-income country settings where the rates of preterm birth are the highest. We conducted a retrospective nested case-control evaluation within a longitudinal study among HIV-uninfected pregnant Kenyan women. To characterize immune function in these women, we evaluated unstimulated and stimulated peripheral blood mononuclear cells in vitro with the A/California/2009 strain of influenza to understand the influenza-induced immune response. We then evaluated transcript expression profiles using the Affymetrix Human GeneChip Transcriptome Array 2.0. Transcriptional profiles of sufficient quality for analysis were obtained from 54 women; 19 of these women delivered <34 weeks and were defined as preterm cases and 35 controls delivered >37 weeks. The median time to birth from sample collection was 13 weeks. No transcripts were significantly associated with preterm birth in a case-control study of matched term and preterm birth (n = 42 women). In the influenza-stimulated samples, expression of IFNL1 was associated with longer time to delivery-the amount of time between sample collection and delivery (n = 54 women). A qPCR analysis confirmed that influenza-induced IFNL expression was associated with longer time to delivery. These data indicate that during pregnancy, ex vivo influenza stimulation results in altered transcriptional response and is associated with time to delivery in cohort of women residing in an area with high preterm birth prevalence.

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Section: Discussionmentioning

confidence: 79%

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confidence: 87%

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

et al. 2020

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“…eQTL results from the GTEx and GEUVADIS data bases for skin tissue and lymphoblastoid cell lines, respectively, support this suggestion. However, to fully investigate this hypothesis, larger sample sizes and further functional follow-up experiments are needed, including fine-mapping of the locus and characterization of pro-inflammatory cytokine signalling shortly before parturition e.g., through non-invasive techniques allowing quantification of cell-free fetal RNA 39,40 and measurement of cytokine levels.…”

Section: Discussionmentioning

confidence: 99%

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 are associated with gestational duration

Liu

Helenius

Skotte

et al. 2018

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The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. We conducted a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 was associated with gestational duration; the association was replicated in 9,291 additional infants (combined P = 3.96 × 10 −14 ). Analysis of 15,536 motherchild pairs showed that the association was driven by fetal rather than maternal genotype. Functional experiments showed that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.

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A Noninvasive Molecular Clock for Fetal Development Predicts Gestational Age and Preterm Delivery

Cited by 2 publications

References 29 publications

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

Influenza-Induced Interferon Lambda Response Is Associated With Longer Time to Delivery Among Pregnant Kenyan Women

Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 are associated with gestational duration

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