The role of bacterial genital infections in spontaneous preterm delivery: a case-control study

Infections are a major threat to human reproductive health, and infections in pregnancy can cause prematurity or stillbirth, or can be vertically transmitted to the fetus leading to congenital infection and severe disease. The acronym ‘TORCH’ (Toxoplasma gondii, other, rubella virus, cytomegalovirus, herpes simplex virus) refers to pathogens directly associated with the development of congenital disease and includes diverse bacteria, viruses and parasites. The placenta restricts vertical transmission during pregnancy and has evolved robust mechanisms of microbial defence. However, microorganisms that cause congenital disease have likely evolved diverse mechanisms to bypass these defences. In this Review, we discuss how TORCH pathogens access the intra-amniotic space and overcome the placental defences that protect against microbial vertical transmission.

Background Most studies of the vaginal microflora have been based on culture or on qualitative molecular techniques. Here we applied existing real-time PCR formats for Lactobacillus crispatus, L. gasseri and Gardnerella vaginalis and developed new formats for Atopobium vaginae, L. iners and L. jensenii to obtain a quantitative non culture-based determination of these species in 71 vaginal samples from 32 pregnant and 28 non-pregnant women aged between 18 and 45 years. Results The 71 vaginal microflora samples of these women were categorized, using the Ison and Hay criteria, as refined by Verhelst et al. (2005), as follows: grade Ia: 8 samples, grade Iab: 10, grade Ib: 13, grade I-like: 10, grade II: 11, grade III: 12 and grade IV: 7. L. crispatus was found in all but 5 samples and was the most frequent Lactobacillus species detected. A significantly lower concentration of L. crispatus was found in grades II (p < 0.0001) and III (p = 0.002) compared to grade I. L. jensenii was found in all grades but showed higher concentration in grade Iab than in grade Ia (p = 0.024). A. vaginae and G. vaginalis were present in high concentrations in grade III, with log10 median concentrations (log10 MC), respectively of 9.0 and 9.2 cells/ml. Twenty (38.5%) of the 52 G. vaginalis positive samples were also positive for A. vaginae. In grade II we found almost no L. iners (log10 MC: 0/ml) but a high concentration of L. gasseri (log10 MC: 8.7/ml). By contrast, in grade III we found a high concentration of L. iners (log10 MC: 8.3/ml) and a low concentration of L. gasseri (log10 MC: 0/ml). These results show a negative association between L. gasseri and L. iners (r = -0.397, p = 0.001) and between L. gasseri and A. vaginae (r = -0.408, p < 0.0001). Conclusion In our study we found a clear negative association between L. iners and L. gasseri and between A. vaginae and L. gasseri. Our results do not provide support for the generally held proposition that grade II is an intermediate stage between grades I and III, because L. gasseri, abundant in grade II is not predominant in grade III, whereas L. iners, abundant in grade III is present only in low numbers in grade II samples.

There is mounting evidence that stress during pregnancy can have detrimental effects on gestation and birth. Existing studies indicate that prenatal stress may increase levels of circulating inflammatory markers that are associated with prematurity and pregnancy complications, suggesting that stress-related changes in the cytokine milieu may increase the risk of poor pregnancy outcome. Previous studies, however, have not clearly connected stress during pregnancy to changes in inflammatory mediators and, in turn, to clinically-relevant outcomes such as premature delivery. The present study sought to directly connect prenatal stress and changes in inflammatory markers to preterm delivery and gestational age at birth (GAB). A sample of 173 women was recruited during the first trimester of pregnancy and followed through delivery. Overall stress, pregnancy-specific distress, and inflammatory markers were assessed early and later in pregnancy, and the predictive value of these measures for preterm birth and GAB was determined. There were significant differences in pregnancy-specific distress, IL-6, and TNF-α between women who delivered prematurely versus those who delivered at term, and elevated levels of pregnancy-specific distress, IL-6, and TNF-α were predictive of shortened GAB overall. Importantly, in many cases, the effects of overall stress and pregnancy-specific distress on GAB were mediated by levels of circulating inflammatory markers. Collectively, these data provide strong evidence that prenatal stress experiences can affect the timing of parturition via alterations in circulating inflammatory mediators, and underscore the need for ongoing research aimed at further understanding the mechanisms and effects of prenatal stress on maternal and infant health. Copyright © 2012 Elsevier Inc. All rights reserved.