Circulating Short-Chain Fatty Acids in Preterm Birth: A Pilot Case-Control Study

Short-chain fatty acids (SCFAs) are by-products from microbial metabolism of fibers with anti-inflammatory effects. SCFAs may mitigate inflammatory conditions such as obesity through modulation of histone acetylation. Lipid metabolism and inflammation play critical roles during pregnancy. However, few studies have examined maternal SCFAs in relation to pregnancy outcomes. This pilot study examined plasma SCFAs in spontaneous preterm birth. This study used stored plasma from an existing cohort to measure seven (proponic acid, methanoic acid, butanoic acid, isovaleric acid, pentanoic acid, methylpropylbutanoic and methylbutanoic acids) SCFAs in 20 women with spontaneous preterm delivery (< 37 weeks gestation) and 30 women with a healthy term delivery (≥ 37 weeks gestation). All women had singleton pregnancies and provided serum at the time of admission to labor and delivery. SCFAs were measured by purge and trap gas chromatography/mass spectrometry. SCFAs were log transformed. Logistic regression with penalized likelihood approach examined associations between SCFAs and preterm birth, adjusting for age, BMI, and race. We also explored if SCFAs had a linear association with pre-pregnancy BMI. Propionic acid had a negative association with preterm birth [odds ratio_adj: 0.56, 95% confidence interval 0.41-0.86). There was a negative association between propionic acid and BMI after adjustments (β = -0.14, p = 0.0011). No other associations were found. Lower levels of propionic acid were associated with preterm birth and correlated with higher BMI. Larger studies should explore if circulatory SCFAs protect against inflammatory pathways during pregnancy and are associated with adverse outcomes when measured earlier in pregnancy.