Amniotic fluid and maternal race influence responsiveness of fetal membranes to bacteria

Abstract

Spontaneous preterm birth (PTB) and preterm prelabor rupture of membranes (pPROM) occur more frequently in African-American women than in other racial groups. This may be due to an enhanced inflammatory response to pathogens associated with the condition. It is also possible that amniotic fluid (AF) has different immunomodulatory properties in African-American women that increase their risk of PTB and pPROM. To test this, we cultured fetal membranes from European-American and African-American women with sterile medium (control), Escherichia coli, Gardnerella vaginalis, Group B streptococci (GBS), Polyporphorans gingivalis, Mycoplasma hominis, Ureaplasma urealyticum or Ureaplasma parvum in the presence and absence of 50% autologous AF. Cytokine concentrations were quantified in the conditioned medium. All bacterial species increased IL-8 production. IL-1β and TNF-α production were stimulated by LPS, E. coli, and G. vaginalis compared with control, but responses to Group B streptococci and P. gingivalis were limited to IL-1β and TNF-α respectively. Genital mycoplasmas stimulated TNF-α and IL-10 but had no effect on IL-1β production. African-Americans had twice the IL-1β response to E. coli as European-Americans (P=0.031). Conversely, European-Americans produced more IL-8 in response to LPS than African-Americans (P=0.026). AF had both pro- and anti-inflammatory properties that varied between races and pathogens. These results suggest that the host response to fetal membrane infections is complex and not generalizable. Interventions to prevent PTB and pPROM may need to be customized based on a patient's race, type of bacterial infection and factors in her AF.

Fig. 1

Racial disparity for cytokine production by fetal membranes. The least squares means ± SEM for IL-1β (A), TNF-α (B), IL-10 (C), and IL-8 (D) production for unstimulated (CTL) and E. coli (EC), Group B streptococci (GBS), G. vaginalis (GV), lipopolysaccharide (LPS), M. hominis (MH), P. gingivalis (PG), U. parvum (UP) or U. urealyticum (UU) stimulated cultures stratified by maternal race. Note that data were log-transformed for analysis and plotted on a log scale for IL-1β and TNF-α. Pairs of bars marked with an asterisk indicate statistically different effects of maternal race (P ≤ 0.05) for that bacterial stimulation. Bars marked with asterisks are significantly different from unstimulated cultures at *P < 0.05, **P < 0.01, and ***P < 0.001.

Fig. 2

Racial disparity in the effect of amniotic fluid (AF) on IL-1β (A) and TNF-α (B) production by fetal membranes. Shown on a log-scale are least-squares means ± SEM for membrane cultures stimulated with medium alone (CTL), E. coli (EC), Group B streptococci (GBS), G. vaginalis (GV), lipopolysaccharide (LPS), M. hominis (MH), P. gingivalis (PG), U. parvum (UP) or U. urealyticum (UU) stratified by race. Pairs of bars marked with asterisks indicate statistically significant effects of AF at *P ≤ 0.05 or **P ≤ 0.01 for that race and bacterial stimulation.

Fig. 3

Racial disparity for the effect of amniotic fluid (AF) on IL-10 (A) and IL-8 (B) production by fetal membranes. Shown are least-squares means ± SEM for membrane cultures stimulated with medium alone (CTL), E. coli (EC), Group B streptococci (GBS), G. vaginalis (GV), lipopolysaccharide (LPS), M. hominis (MH), P. gingivalis (PG), U. parvum (UP) or U. urealyticum (UU) stratified by race. Bars marked with asterisks indicate statistically significant effects of AF at *P 0.05 ≤ or **P ≤ 0.01 for that race and bacterial stimulation.

Fig. 4

Racial disparity in the effect of amniotic fluid on IL-1b (A) and TNF-α (B) production by fetal membranes. Shown are least-squares means ± SEM for membrane cultures stimulated with medium alone (CTL), or cultures stimulated with E. coli (EC), Group B Streptococci (GBS), G. vaginalis (GV)-, Lippopolysaccharide (LPS), M. hominis (MH), P. gingivalis (PG), U. parvum (UP) or U. urealyaticum (UU) stratified by race. Pairs of bars marked with asterisks indicate statistically significant effects of amniotic fluid at *P < 0.05 or **P < 0.01 for that race and bacterial stimulation.

Fig. 5

Racial disparity for the effect of amniotic fluid on IL-8 (A) and IL-10 (B) production by fetal membranes. Shown are least-squares means ± SEM for membrane cultures stimulated with medium alone (CTL), or cultures stimulated with E. coli (EC), Group B Streptococci (GBS), G. vaginalis (GV), Lippopolysaccharide (LPS), M. hominis (MH), P. gingivalis (PG), U. parvum (UP) or U. urealyaticum (UU) stratified by race. Bars marked with asterisks indicate statistically significant effects of amniotic fluid at *P < 0.05 or **P < 0.01 for that race and bacterial stimulation.