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Problem Inflammatory cytokines and matrix metalloproteinases (MMPs) contribute to preterm labor pathophysiology. The objective of this study was to test anti-inflammatory properties of simvastatin in human fetal membranes exposed to lipopolysaccharide (LPS). Method of study Normal term human fetal membrane explants (n = 11) were allocated to one of the six study groups: control, LPS only (100 ng/mL), simvastatin only (125 ng/mL), simvastatin given 6 hrs prior to LPS (S-L), simvastatin given 6 hrs post-LPS (L-S), and simvastatin and LPS given simultaneously (L+S). Explants were incubated for 24 hrs. Multiplex ELISA for cytokines: IL-1β, IL-6, IL-10, and TNF-α; soluble cytokine receptors: sIL-1R2, sIL-6R, sTNFR1, and R2; MMPs (1, 2, 7, 9, and 10); and tissue inhibitor of metalloproteinase-2 (TIMP-2) was performed on tissue culture supernatants. Pairwise comparison between different groups was conducted by least square mean estimates. Results Compared with controls, LPS stimulation increased cytokine production and their tissue bioavailability (measured as the molar ratio of cytokine to its soluble receptor), thus confirming membrane immune reactivity (P

Objective To determine the risk of gestational diabetes mellitus (GDM) and insulin resistance (IR) in obesity defined by body mass index (BMI), waist-to-hip ratio (WHR), or both combined. Methods Secondary analysis of a randomized multicenter trial of antioxidant supplementation versus placebo in nulliparous low-risk women to prevent pregnancy associated hypertension. Women between 9 and 16 weeks with data for WHR and BMI were analyzed for GDM ( n = 2,300). Those with fasting glucose and insulin between 22 and 26 weeks ( n = 717) were analyzed for IR by homeostatic model assessment of IR (normal, ≤ 75th percentile). WHR and BMI were categorized as normal (WHR, 2 ); overweight (WHR, 0.8–0.84; BMI, 25–29.9 kg/m 2 ); and obese (WHR, ≥ 0.85; BMI ≥ 30 kg/m 2 ). Receiver operating characteristic curves and logistic regression models were used. Results Compared with normal, the risks of GDM or IR were higher in obese by BMI or WHR. The subgroup with obesity by WHR but not by BMI had no increased risk of GDM. BMI was a better predictor of IR (area under the curve [AUC]: 0.71 [BMI], 0.65 [WHR], p = 0.03) but similar to WHR for GDM (AUC: 0.68 [BMI], 0.63 [WHR], p = 0.18). Conclusion Increased WHR and BMI in early pregnancy are associated with IR and GDM. BMI is a better predictor of IR compared with WHR. Adding WHR to BMI does not improve its ability to detect GDM or IR.