N,N-dimethylacetamide blocks inflammation-induced preterm birth and remediates maternal systemic immune responses.

The common excipient, N,N-dimethylacetamide (DMA), prevents imminent endotoxin-induced preterm birth in mice. The present study hypothesized that DMA forestalls preterm birth to term (defined as day 18.5 or later) by attenuating bacterial endotoxin lipopolysaccharide (LPS)-induced maternal systemic inflammatory responses and cervix remodeling. Accordingly, LPS (i.p.) on day 15 postbreeding stimulated preterm delivery within 24 h while mice treated with DMA 2 h preceding and 9 h following LPS administration remained pregnant, comparable to saline and DMA controls, to deliver viable pups at term. Irrespective of LPS or DMA + LPS treatment, maternal plasma pro- and anti-inflammatory cytokines on day 15.5 (12 h post-LPS) increased tenfold compared to baseline concentrations in controls. On day 16 of pregnancy, plasma concentrations of G-CSF and TNFα were statistically significantly reduced in the prepartum LPS + DMA group compared to those in postpartum mice given LPS. By day 18 of pregnancy, all cytokines returned to baseline-equivalent to low systemic levels throughout the study in saline and DMA controls that gave birth at term. In addition, maternal plasma progesterone declined within 12 h in prepartum LPS-treated mice to postpartum concentrations on day 16. Although a similar transient decrease occurred by 12 h in DMA + LPS mice, plasma progesterone returned to baseline concentrations in controls. Contemporaneously, the progression of prepartum cervix remodeling leading to preterm delivery was acutely forestalled by DMA without impeding birth at term. These findings support the hypothesis that DMA not only prevents inflammation-driven preterm birth, but rescues pregnancy for birth to occur at term. The results raise the possibility that maternal signals can forecast risk of preterm birth while selective suppression of systemic inflammation can mitigate adverse pregnancy outcomes.