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110: N-acetylcysteine prevents preterm birth in an intrauterine inflammatory model of preterm labor

      Objective

      Intrauterine infection is strongly associated with preterm birth particularly at early gestations. Additionally, it is associated with an increased risk of neurologic impairment in survivors. We hypothesized that NAC, a potent anti-inflammatory and antioxidant, would decrease preterm birth and evidence of maternal and fetal inflammation in an infectious model of preterm birth.

      Study Design

      On day 15, timed-pregnant CD-1 mice were given LPS (100 g) or saline via intrauterine injection. They also were randomly assigned to receive either subcutaneous NAC (100 mg/kg) or saline 60 minutes prior to LPS administration. Animals were monitored until delivery. In another set of NAC-treated and untreated animals, LPS or saline was given and the animals were sacrificed at 6 hours and myometrium, placenta, and fetal brain were collected. RT-PCR was performed to determine the expression of IL-6 in these tissues. RT-PCR for expression of TNF- in fetal brain was also performed.

      Results

      Intrauterine LPS administration is associated with a high rate of preterm delivery within 24 hours compared with controls (79% vs 0%, p < .005). NAC treatment significantly reduced preterm delivery [0.45 (95% CI: 0.26-0.83), p<.008]. Additionally, LPS administration was associated with an increased expression of IL-6 in myometrium (p<.03) and the placenta (p<.001). This effect was significantly attenuated with NAC in myometrium (p<.039). There was a non-significant increase in IL-6 in the fetal brain and a significant increase in TNF- (<0.01) with LPS adminstration. NAC treatment was associated with a non-significant reduction in TNF- expression.

      Conclusion

      NAC reduces preterm birth in this animal model and may reduce the maternal response in the setting of intrauterine inflammation. Further investigation is warranted to determine whether it can be useful in the prevention of preterm birth.