Faculty Bibliography

OBJECTIVE:Factors influencing intraamniotic adiponectin levels and their functional significance remain incompletely elucidated. We prospectively measured adiponectin in amniotic fluid and identified its associations with maternal parameters, mediators in amniotic fluid and pregnancy outcomes. STUDY DESIGN/METHODS:Mid-trimester amniotic fluid from 571 women was tested for adiponectin, interleukin (IL)-6, IL-8 and α-amylase by enzyme-linked immunosorbant assay (ELISA), after which clinical data were obtained. Correlations between adiponectin and clinical or laboratory variables were analyzed by the Kruskal-Wallis, Mann-Whitney and Spearman rank correlation tests. RESULTS:As compared to median levels in 462 women with a term delivery (7.8 ng/mL), adiponectin was elevated in 14 women who subsequently developed preterm premature rupture of membranes (pPROM) (17.3 ng/mL) and 24 women with an iatrogenic preterm birth (IPTB) (13.9 ng/mL) (P=0.0003), but not in 30 women who subsequently had a spontaneous preterm birth with intact membranes (8.1 ng/mL) (P>0.05). Median adiponectin was also elevated in 13 women whose babies developed fetal growth restriction (FGR) (20.6 ng/mL) (P=0.0055) and in 22 women whose babies had respiratory distress syndrome (RDS) (23.0 ng/mL) (P<0.0001). The adiponectin concentration was positively correlated with amylase (P=0.0089) and inversely correlated with maternal body mass index (P=0.0045). CONCLUSION/CONCLUSIONS:Adiponectin is a component of mid-trimester amniotic fluid and its concentration varies with maternal body mass index and subsequent development of pPROM, IPTB, FGR and RDS.

Epithelial cells lining the vagina are major components of genital tract immunity. The influence of the vaginal microbiome on properties of host epithelial cells is largely unexplored. We evaluated whether differences in the most abundant lactobacilli species or bacterial genera in the vagina of first trimester pregnant women were associated with variations in the extent of stress and autophagy in vaginal epithelial cells. Vaginal swabs from 154 first trimester pregnant women were analyzed for bacterial composition by amplification and sequencing of the V1-V3 region of bacterial 16S rRNA genes. Vaginal epithelial cells were lysed and autophagy quantitated by measurement of p62. Intracellular levels of the inducible 70kDa heat shock protein (hsp70), an indicator of cell stress and an autophagy inhibitor, were determined. When Lactobacillus crispatus was the most abundant member of the vaginal microbiota, epithelial p62 and hsp70 levels were lowest as compared to when other bacterial taxa were most abundant. The highest concentrations of p62 and hsp70 were associated with Streptococcus and Bifidobacterium abundance. The p62 level associated with Gardnerella abundance was lower than that observed when lactobacilli other than L. crispatus were most abundant. In conclusion, in the first trimester of pregnancy the abundance of different bacterial taxa is associated with variations in autophagy and magnitude of the stress response in vaginal epithelial cells.

Pregnancy permanently alters maternal anatomy, physiology and immunity. We evaluated if the vaginal microbiome differed between women with a first or subsequent conception. Relative abundance of bacteria in the vaginal microbiome in first trimester pregnant women, 52 with their first known conception, 26 with a prior spontaneous or induced abortion but no deliveries and 77 with at least one prior birth, was determined by classifying DNA sequences from the V1-V3 region of bacterial 16 S rRNA genes. Lactobacillus crispatus was the numerically most abundant bacterium in 76.4% of women with a first conception, 50.0% with only a prior spontaneous or scheduled abortion and 22.2% with a prior birth (p ≤ 0.01). L. iners was the most abundant bacterium in 3.8% of women with a first conception as compared to 19.2% (p = 0.03) and 20.8% (p = 0.03) in those with a prior abortion or birth, respectively. Gardnerella as the most abundant bacterial genus increased from 3.8% in women with a first conception to 15.4% and 14.3% in those with a prior abortion or birth, respectively (p > 0.05). L. iners dominance was also associated with a history of spontaneous abortion (p ≤ 0.02). The composition of the vaginal microbiome and its influence on pregnancy outcome varies with pregnancy history.