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

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.

Integrated trajectories of the maternal metabolome, proteome, and immunome predict labor onset

“…The observed dampening of systemic inflammatory events with approaching labor contrasts with prior studies showing increased local inflammation of the cervix, decidua, fetal membranes, and placenta during labor and parturition (46,69,70), although several other studies of systemic immune responses during pregnancy echo our findings of decreased peripheral immune cell responses with approaching labor (47,56,57,60,71,72). Hence, the systemic dampening of pro inflammatory responses may be important to keep in check pro inflammatory events initiated locally with labor onset.…”

“…Current efforts to monitor biological adaptations during pregnancy have primarily been focused on investigating dynamics that differentiate normal from pathological pregnancies on the basis of GA (12,13,(47)(48)(49)(50)(51)(52)(53). Although they are informative in characterizing pathological deviations during pregnancy, these approaches provide limited information for the prediction of timing of labor because they rely on estimates of GA, which are imposed by human assumption rather than based on biological determination.…”