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168: Impaired anti-inflammatory response in women with a prior spontaneous preterm birth

      Objective

      To examine whether differences in host immune response to antigen stimulation may explain risk for prior spontaneous preterm birth (SPTB).

      Study Design

      Peripheral blood mononuclear cells (PBMC) were isolated from non-pregnant women enrolled in a follow-up study of maternal-infant dyads 5-8 years after a SPTB (n=39) or indicated preterm birth (IPTB, n=26) at 23-31 6/7 weeks and term birth at 37 weeks (n=11). Cells were stimulated with LPS (1.0 μg/ml), incubated 24 hours, and supernatant assayed for cytokines using Luminex x100 (Luminex Corp, Austin, TX) including: Th1 (IFN-, IL-2, IL-12p70); Th2 (IL-4, IL-5, IL-10); general pro-inflammatory (IL-1, IL-6, IL-8, TNF-). Cytokines were considered elevated if >75%ile for the term (control) group.

      Results

      The cohort was 65% black and 34% white. The mean maternal age at delivery was 24±5 yrs; at follow-up 30±3 yrs. The mean GA at delivery was 29±2 in the SPTB, 29±2 in the IPTB, and 40±1 wks in the term group. No differences were noted in median levels of individual cytokines among birth groups except IL-4 (0.7 vs 1.8 pg/ml, p=0.02) and IL-5 (1.97 vs 2.5 pg/ml, p=0.03) levels were lower in the SPTB vs IPTB group. When evaluating the panel of Th1 or Th1+general pro-inflammatory cytokines, there were no differences among birth groups in the proportion with elevated levels. For the Th2 panel (generally considered anti-inflammatory), women with a prior SPTB were more likely to have none (0/3) of the cytokine levels elevated when compared to IPTB and term (none of Th2 cytokines >75%ile: SPTB 69.2 vs IPTB 34.6 and term 27.3%, p=0.005).

      Conclusion

      In this cohort of women followed-up 5-8 years after delivery, a prior SPTB was associated with less anti-inflammatory cytokine response after antigen stimulation when compared to women with a prior IPTB or term birth. These findings suggest an altered ability to regulate inflammation in women with a prior SPTB.