The Maternal Serological Response to Intrauterine Ureaplasma sp. Infection and Prediction of Risk of Pre-Term Birth

Abstract

Pre-term birth (PTB) associated with intrauterine infection and inflammation (IUI) is the major cause of early PTB less than 32 weeks of gestation. Ureaplasma spp. are common commensals of the urogenital tract in pregnancy and are the most commonly identified microorganisms in amniotic fluid of pre-term pregnancies. While we have an understanding of the causal relationship between intra-amniotic infection, inflammation and PTB, we are still unable to explain why vaginal Ureaplasma sp. colonization is tolerated in some women but causes PTB in others. It is now known that placental tissues are frequently colonized by bacteria even in apparently healthy pregnancies delivered at term; usually this occurs in the absence of a significant local inflammatory response. It appears, therefore, that the site, nature, and magnitude of the immune response to infiltrating microorganisms are key in determining pregnancy outcome. Some evidence exists that the maternal serological response to Ureaplasma sp. colonization may be predictive of adverse pregnancy outcome, although issues such as the importance of virulence factors (serovars) and the timing, magnitude, and functional consequences of the immune response await clarification. This mini-review discusses the evidence linking the maternal immune response to risk of PTB and the potential applications of maternal serological analysis for predicting obstetric outcome.

A specific bacterial DNA signature in the vagina of Australian women in midpregnancy predicts high risk of spontaneous preterm birth (the Predict1000 study)

“…Discussion of these is beyond the scope of this study but has been reviewed by Ireland and Keelan. 82 A previous exposure to U parvum in terms of vaginal colonization does not seem to predispose pregnant women to increased risk of PTB based on specific T-cell 83 or monocyte 84 responses in the blood; however, power was limited in both of these studies.…”

Placing Ureaplasma within the Context of Bronchopulmonary Dysplasia Endotypes and Phenotypes

“…These virulence factors evade the host immune response and can cause tissue damage [42]. The immune system then reacts producing cytokines such as tumor necrosis factor α, interleukin (IL)-6, IL-8, or IL-10 [44], activating the nuclear factor kappa B (NFkB) pathway via toll-like receptors (TLR)-1, TLR-2, and TLR-6 [45], stimulating macrophage activity through TLR-2 and TLR-4 [46], and increasing an immunoglobulin response [47]. At least part of this immune response has a protective character [47].…”

“…The immune system then reacts producing cytokines such as tumor necrosis factor α, interleukin (IL)-6, IL-8, or IL-10 [44], activating the nuclear factor kappa B (NFkB) pathway via toll-like receptors (TLR)-1, TLR-2, and TLR-6 [45], stimulating macrophage activity through TLR-2 and TLR-4 [46], and increasing an immunoglobulin response [47]. At least part of this immune response has a protective character [47]. Another protective mechanism shown in in vitro models is surfactant protein A, which clears Ureaplasma in mouse lungs [48].…”

Perinatal Infections With Ureaplasma

“…Despite some discrepancy between studies, the detection of Ureaplasma IgG in maternal sera together with amniotic fluid colonization is considered as predictive of an increased risk of developing pregnancy complications [odds ratio: 81.00 at genetic amniocentesis ( P = 0.04); odds ratio: 24.56 ( P = 0.04); and RR: 2.31 ( P = 0.02) at PPROM]. 25 However, little is known about IgG titers and/or IgG subclass inducing these deleterious effects. In contrast to data on Ureaplasma induced humoral responses, knowledge on Ureaplasma induced T-cell responses is very limited.…”