Abstract
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.
Highlights
Preterm birth, defined as birth before the 37th week of gestation, is a highly prevalent disorder of pregnancy that is a major driver of childhood morbidity and mortality [1,2,3,4]
Participants were eligible for inclusion in this substudy if they had a peripheral blood mononuclear cell (PBMC) sample collected at their enrollment visit during pregnancy with 2 aliquots available
To assess whether there were significant changes in expression patterns of transcripts between the women who gave birth preterm vs. those who gave birth at term in an area of high prevalence of preterm birth, we used PBMCs from 42 women enrolled in the Mama Salama study in Kisumu, Kenya in whom we obtained sufficient quality RNA
Summary
Preterm birth, defined as birth before the 37th week of gestation, is a highly prevalent disorder of pregnancy that is a major driver of childhood morbidity and mortality [1,2,3,4]. Preterm birth is divided into categories based on timing: extremely preterm (before 28 weeks), very preterm (28–32 weeks), and moderate to late preterm (32–37 weeks) These categories may differ in their pathogenic underpinnings, which can include genetic factors, multiple pregnancies, infections, and chronic conditions such as diabetes and high blood pressure [5, 6]. It is possible that immune mechanisms play a significant role in driving preterm birth, an idea supported by the fact that many of the known risk factors for preterm birth alter immune function. Consistent with this idea, several studies have demonstrated that preterm birth is associated with altered inflammatory responses, detectable in the placenta and in the amniotic fluid [5]. A recent study demonstrated that activated T cells are found at the maternal-fetal interface in women with spontaneous preterm delivery, and that, in a mouse model, treatment with progesterone can attenuate this inflammation and reduce risk of preterm birth [18]
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